Drug-Induced Liver Injury
Wounds and Injuries
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Liver Diseases, Alcoholic
Liver Function Tests
Spinal Cord Injuries
Drug-Induced Liver Injury, Chronic
Liver Failure, Acute
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)
Injury Severity Score
Disease Models, Animal
Liver Cirrhosis, Experimental
Cytochrome P-450 CYP2E1
An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.
Acute Lung Injury
A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Hepatic Stellate Cells
Acute Kidney Injury
Liver Cirrhosis, Alcoholic
Fatty Liver, Alcoholic
Tumor Necrosis Factor-alpha
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Abbreviated Injury Scale
Classification system for assessing impact injury severity developed and published by the American Association for Automotive Medicine. It is the system of choice for coding single injuries and is the foundation for methods assessing multiple injuries or for assessing cumulative effects of more than one injury. These include Maximum AIS (MAIS), Injury Severity Score (ISS), and Probability of Death Score (PODS).
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Myocardial Reperfusion Injury
Head Injuries, Closed
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
Soft Tissue Injuries
Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as "soft tissue injuries of the hand".
Diffuse Axonal Injury
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Carotid Artery Injuries
Damages to the CAROTID ARTERIES caused either by blunt force or penetrating trauma, such as CRANIOCEREBRAL TRAUMA; THORACIC INJURIES; and NECK INJURIES. Damaged carotid arteries can lead to CAROTID ARTERY THROMBOSIS; CAROTID-CAVERNOUS SINUS FISTULA; pseudoaneurysm formation; and INTERNAL CAROTID ARTERY DISSECTION. (From Am J Forensic Med Pathol 1997, 18:251; J Trauma 1994, 37:473)
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Rats, Inbred Strains
Gene Expression Regulation
Vascular System Injuries
Injuries to blood vessels caused by laceration, contusion, puncture, or crush and other types of injuries. Symptoms vary by site and mode of injuries and may include bleeding, bruising, swelling, pain, and numbness. It does not include injuries secondary to pathologic function or diseases such as ATHEROSCLEROSIS.
A condition produced by a deficiency of CHOLINE in animals. Choline is known as a lipotropic agent because it has been shown to promote the transport of excess fat from the liver under certain conditions in laboratory animals. Combined deficiency of choline (included in the B vitamin complex) and all other methyl group donors causes liver cirrhosis in some animals. Unlike compounds normally considered as vitamins, choline does not serve as a cofactor in enzymatic reactions. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Dose-Response Relationship, Drug
Trauma Severity Indices
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Drugs, Chinese Herbal
Reverse Transcriptase Polymerase Chain Reaction
End Stage Liver Disease
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
A widely used anti-inflammatory agent isolated from the licorice root. It is metabolized to GLYCYRRHETINIC ACID, which inhibits 11-BETA-HYDROXYSTEROID DEHYDROGENASES and other enzymes involved in the metabolism of CORTICOSTEROIDS. Therefore, glycyrrhizic acid, which is the main and sweet component of licorice, has been investigated for its ability to cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure, as well as depression of the renin-angiotensin-aldosterone system.
Bile Acids and Salts
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Smoke Inhalation Injury
Nitric Oxide Synthase Type II
Hep G2 Cells
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Head Injuries, Penetrating
Severity of Illness Index
Thiobarbituric Acid Reactive Substances
Recovery of Function
In Situ Nick-End Labeling
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
Central Nervous System Depressants
Analysis of Variance
Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease. (1/2195)Lymphocyte proliferation inhibitory factor (PIF) was determined in the supernatants of PHA-stimulated lymphocytes from patients with alcoholic liver disease. PIF was assayed by determining inhibition of DNA synthesis in WI-38 human lung fibroblasts. A two-fold greater inhibition in thymidine incorporation into DNA by lung fibroblasts was observed in supernatants of PHA stimulated lymphocytes from patients with alcoholic hepatitis or active Laennec's cirrhosis as compared with that found in control subjects or patients with fatty liver. It is suggested that decreased liver cell regeneration seen in some patients with alcoholic hepatitis may be due to increased elaboration of PIF. (+info)
Structural and functional changes in acute liver injury. (2/2195)Carbon tetrachloride produces liver cell injury in a variety of animal species. The first structurally recognizable changes occur in the endoplasmic reticulum, with alteration in ribosome-membrane interactions. Later there is an increase in intracellular fat, and the formation of tangled nets of the ergastoplasm. At no time are there changes in mitochondria or single membrane limited bodies in cells with intact plasmalemma, although a relative increase in cell sap may appear. In dead cells (those with plasmalemma discontinuties) crystalline deposits of calcium phosphatase may be noted. Functional changes are related to the endoplasmic reticulum and the plasma membrane. An early decrease in protein synthesis takes place; an accumulation of neutral lipid is related to this change. Later alterations in the ergastoplasmic functions (e.g., mixed function oxidation) occurs. Carbon tetrachloride is not the active agent; rather, a product of its metabolism, probably the CC1, free radical, is. The mechanisms of injury include macromolecular adduction and peroxide propagation. A third possibility includes a cascade effect with the production of secondary and tertiary products, also toxic in nature, with the ability to produce more widespread damage to intracellular structures. (+info)
Various forms of chemically induced liver injury and their detection by diagnostic procedures. (3/2195)A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities. (+info)
Quantitative aspects in the assessment of liver injury. (4/2195)Liver function data are usually difficult to use in their original form when one wishes to compare the hepatotoxic properties of several chemical substances. However, procedures are available for the conversion of liver function data into quantal responses. These permit the elaboration of dose-response lines for the substances in question, the calculation of median effective doses and the statistical analysis of differences in liver-damaging potency. These same procedures can be utilized for estimating the relative hazard involved if one compares the liver-damaging potency to the median effective dose for some other pharmacologie parameter. Alterations in hepatic triglycerides, lipid peroxidation, and the activities of various hepatic enzymes can also be quantitiated in a dose-related manner. This permits the selection of equitoxic doses required for certain comparative studies and the selection of doses in chemical interaction studies. The quantitative problems involved in low-frequency adverse reactions and the difficulty these present in the detection of liver injury in laboratory animals are discussed. (+info)
Assessment of hepatotoxic potential. (5/2195)Philosophic concepts and pragmatic approaches toward improved understanding of the effect of drugs in the hepatocyte are reviewed. No set pattern of studies is advocated but rather observations are encouraged within the framework of studies that provide for varied exposure of the hepatocyte. Clinical usage should be imitated to provide earliest possible indications of toxicity in man. The need for definitive characterization through utilization of appropriate methodology derived from cross-fertilization of related disciplines is stressed. Both minimal and maximal dose effects should be established. Selected use of electron microscopy has become essential for characterizing responses of the liver to injury. The advantages of the toluidine blue-stained Epon "thick" sections are emphasized. Such observations are used to implement the utility of serial biopsies from the beagle dog prior to and during long-term study of potential hepatic injury. Examples of the critical effects of drug concentration within the hepatocyte are presented. (+info)
Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro. (6/2195)The acute hepatotoxicity induced by alpha-naphthylisothiocyanate (ANIT) in rats is manifested as neutrophil-dependent necrosis of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. This hepatotoxicity mirrors that of drug-induced cholangiolitic hepatitis in humans. Since BDECs are primary targets of ANIT-induced toxicity, we hypothesized that after exposure to ANIT, BDECs produce a factor(s) that causes neutrophil chemotaxis and neutrophil-dependent hepatocellular injury. To test this hypothesis BDECs were isolated from male Sprague Dawley rats and incubated with ANIT (6.25, 12.5, 25, or 50 microM) or vehicle for 24 h. The conditioned medium (CM) was collected and placed in the bottom chamber of a two-chambered chemotaxis system, while isolated neutrophils were placed in the top chamber. Chemotaxis was indicated by neutrophil migration through a membrane to the bottom chamber. CM from BDECs exposed to each concentration of ANIT was chemotactic, whereas CM from vehicle-treated BDECs was not. ANIT alone caused a modest degree of chemotaxis at 50 microM. The conditioned media were added to isolated hepatocytes or to hepatocyte-neutrophil cocultures and incubated for 24 h. Hepatocyte toxicity was indicated by alanine aminotransferase release into the culture medium. CM from vehicle-treated BDECs did not cause hepatocyte killing in either hepatocyte-neutrophil cocultures or hepatocyte cultures. In contrast, the addition of CM from ANIT-treated BDECs (CM-BDEC-A) to hepatocyte-neutrophil cocultures resulted in hepatocyte killing. The same CM was not cytotoxic to hepatocyte cultures devoid of neutrophils. The hepatocyte killing could not be explained by residual ANIT in the CM, which was below the limit of detection (< or = 0.5 microM). The addition of antiproteases afforded protection against neutrophil-dependent hepatocellular injury induced by CM-BDEC-A. These results indicate that ANIT causes BDECs to release a factor(s) that attracts neutrophils and stimulates them to injure hepatocytes in vitro. (+info)
Effect of central corticotropin-releasing factor on carbon tetrachloride-induced acute liver injury in rats. (7/2195)Central neuropeptides play important roles in many instances of physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors and sympathetic nerve activation are reported to exacerbate experimental liver injury. Some stressors are known to stimulate corticotropin-releasing factor (CRF) synthesis in the central nervous system and induce activation of sympathetic nerves in animal models. The effect of intracisternal CRF on carbon tetrachloride (CCl4)-induced acute liver injury was examined in rats. Intracisternal injection of CRF dose dependently enhanced elevation of the serum alanine aminotransferase (ALT) level induced by CCl4. Elevations of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by CCl4 were also enhanced by intracisternal CRF injection. Intracisternal injection of CRF also aggravated CCl4-induced hepatic histological changes. Intracisternal CRF injection alone did not modify the serum ALT level. Intravenous administration of CRF did not influence CCl4-induced acute liver injury. The aggravating effect of central CRF on CCl4-induced acute liver injury was abolished by denervation of hepatic plexus with phenol and by denervation of noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch vagotomy or atropine treatment. These results suggest that CRF acts in the brain to exacerbate acute liver injury through the sympathetic-noradrenergic pathways. (+info)
Influences of Kupffer cell stimulation and suppression on immunological liver injury in mice. (8/2195)AIM: To study the possible involvement of Kupffer cells (KC) in immunological liver injury in mice. METHODS: Liver injury was induced by i.v. injection of Bacillus Calmette-Guerin (BCG) 5 x 10(7) viable bacilli followed by i.v. injection of lipopolysaccharides (LPS) 7.5 micrograms to each mouse. Indian ink and silica were i.v. injected to suppress KC and retinol was given po to stimulate KC in these mice. Plasma alanine aminotransferase (AlaAT), aspatate aminotransferase (AspAT), nitric oxide (NO), and liver tissue were examined. RESULTS: Injection of LPS following BCG injection resulted in a remarkable elevation of plasma NO, AlaAT, and AspAT levels, and severe liver damage. The damages were enhanced by the activation of KC with retinol and reduced by suppression of KC with silica and Indian ink. CONCLUSION: The degree of liver injury induced by BCG + LPS is closely correlated with the status of KC, and NO from KC plays an important role in the pathogenesis of the liver damage in mice. (+info)
Drug-induced liver injury | Article about drug-induced liver injury by The Free Dictionary
Looking for drug-induced liver injury? Find out information about drug-induced liver injury. Law a violation or infringement of another persons rights that causes him harm and is actionable at law A structural or functional stress or trauma that... Explanation of drug-induced liver injury
Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa
SCHUTZ, Charlotte et al. Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa. SAMJ, S. Afr. med. j. [online]. 2012, vol.102, n.6, pp.507-511. ISSN 2078-5135.. BACKGROUND: G F Jooste Hospital (GFJH) is a secondary-level referral hospital in a high HIV and tuberculosis (TB) co-infection setting. AIMS: To assess the proportion of significant drug-induced liver injury (DILI) due to tuberculosis treatment (TBT) and/or antiretroviral therapy (ART) among patients presenting with liver dysfunction at GFJH and to describe management and outcomes. METHODS: A retrospective observational study was performed of all cases referred to GFJH with significant liver dysfunction from 1 January to 30 June 2009. Significant liver dysfunction was defined by alanine transaminase (ALT)=200 U/l or total bilirubin (TBR)=44 µmol/l. TBT- or ART-associated DILI was defined as significant liver dysfunction attributed to TBT and/or ART and which resulted in the ...
Impact of single nucleotide polymorphisms on severe hepatotoxicity induced by gefitinib or erlotinib in non-small cell lung...
Among the 66 patients, 60 received gefitinib (Group A) and 27 received erlotinib (Group B). 21 were treated with both gefitinib and erlotinib at different times. Severe hepatotoxicity was detected in 19 (32%) from Group A and 6 (22%) from Group B. Poor metabolizer (PM) was defined as homozygous of variant allele (SNPs) which reduced metabolic enzyme activity. The phenotypes were as follows: CYP3A5, PM/ non-PM = 34/ 32; CYP2D6, PM/ non-PM = 5/ 61; and VKORC1, PM/ non-PM = 55/ 11. In Group A, severe hepatotoxicity rate was significantly higher among patients with PM for CYP3A5 (PM vs. non-PM: 48% vs. 14%; p < 0.01), PM for CYP2D6 (PM vs. non-PM: 80% vs. 27%; p = 0.04) and non-PM for VKORC1 (PM vs. non-PM: 26% vs. 67%; p = 0.02). In Group B, any types of SNPs were not correlated with severe hepatotoxicity rate. Among 8 patients whose treatments were changed from gefitinib to erlotinib because of severe hepatotoxicity at the initial EGFR-TKI treatment, 7 patients exhibited an improvement of ...
Hepatotoxicity - Cancer Therapy Advisor
Chalasani, NP, Hayashi, PH, Bonjovsky, HL. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol.. vol. 109. 2014. pp. 950-966. (Recently published clinical guidelines by the ACG on the diagnosis and management of DILI). Chalasani, N, Fontana, RJ, Bonkovsky, HL. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. vol. 135. 2008. pp. 1924-1934. (This study from the NIH-sponsored Drug-Induced Liver Injury Network (DILIN) reports on the prospective analysis of 300 patients within the United States who were diagnosed with DILI.). Andrade, RJ, Lucena, MI, Fernandez, MC. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish Registry over a 10-year period. Gastroenterology. vol. 129. 2005. pp. 512-521. (This work is another large prospective analysis of more than 400 DILI cases.). Bjornsson, E, Jacobsen, EI, Kalaitzakis, E. ...
Drug-Induced Liver Injury Is On The Rise - Redorbit
More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. This type of liver injury results from the use of certain prescription and over-the-counter medications, as well as dietary supplements, and is among the more challenging forms of liver disease due to its difficulty to predict, diagnose and manage.. Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 inhabitants, per year. These results are significantly higher than the last population-based study of this kind, conducted in France from 1997-2000, which reported 13.9 cases per 100,000 inhabitants, per year.. The most commonly implicated drugs were amoxicillin-clavulante (penicillin used to fight bacteria), azathioprine (an immunosuppressive drug used in organ transplantation and autoimmune diseases) and infliximab (also used to ...
Mass. General researchers find novel way to prevent drug-induced liver injury - Massachusetts General Hospital, Boston, MA
Developing, approving and prescribing a drug requires that the therapeutic benefits be weighed against any potential toxicities. Liver toxicity limits the development of many therapeutic compounds and presents major challenges to both clinical medicine and to the pharmaceutical industry. Drug-induced liver injury is the most common cause of acute liver failure in the U.S. and is also the most frequent reason for abandoning drugs early in development or withdrawing them from the market. Since no pharmaceutical strategies currently exist for preventing drug-induced liver injury, treatment options are limited to discontinuing the offending drug, supportive care and transplantation for end-stage liver failure ...
GastroHep News Story
Of these, 3% were referred for evaluation to the out-patient clinic whereas 3% had a follow-up after hospitalization of drug-induced liver injury.. The median age was 58 years, and 56% were females.. The investigators observed a hepatocellular pattern in 48%, cholestatic in 40% and mixed in 12% of cases.. The team noted that antibiotics were the most common agents causing drug-induced liver injury followed by non-steroidal anti-inflammatory drugs.. Diclofenac most often responsible for the drug-induced liver injury.. Dr de Valles team concludes, Drug-induced liver injury cases constituted 6% of all out-patients and 3% of referrals and occurred more often in women. Antibiotics and diclofenac were the most common causes of drug-induced liver injury among out-patients. ...
Drug-induced hepatitis. Causes, symptoms, treatment Drug-induced hepatitis
Description of disease Drug-induced hepatitis. Treatment Drug-induced hepatitis. Symptoms and causes Drug-induced hepatitis Prophylaxis Drug-induced hepatitis
Prediction and mechanistic analysis of drug-induced liver injury (DILI) based on chemical structure | Biology Direct | Full Text
Drug-induced liver injury (DILI) is a major safety concern characterized by a complex and diverse pathogenesis. In order to identify DILI early in drug development, a better understanding of the injury and models with better predictivity are urgently needed. One approach in this regard are in silico models which aim at predicting the risk of DILI based on the compound structure. However, these models do not yet show sufficient predictive performance or interpretability to be useful for decision making by themselves, the former partially stemming from the underlying problem of labeling the in vivo DILI risk of compounds in a meaningful way for generating machine learning models. As part of the Critical Assessment of Massive Data Analysis (CAMDA)
Emerging hepatotoxicity biomarkers and their potential to improve understanding and management of drug-induced liver injury |...
Biomarkers of drug-induced liver injury (DILI) are essential for the diagnosis of severe cases of DILI in clinical trials and clinical practice, but the currently used biomarker paradigm detects damage after it has occurred and has limited prognostic value. The development of new biomarker strategies that improve the diagnosis of DILI by providing increased specificity and/or by identifying individual patients who are at risk for DILI is therefore crucial. See related Research, http://genomemedicine.com/content/5/9/86
Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study<...
TY - JOUR. T1 - Features and outcomes of 899 patients with drug-induced liver injury. T2 - The DILIN prospective study. AU - Chalasani, Naga. AU - Bonkovsky, Herbert L.. AU - Fontana, Robert. AU - Lee, William. AU - Stolz, Andrew. AU - Talwalkar, Jayant. AU - Reddy, K. Rajendar. AU - Watkins, Paul B.. AU - Navarro, Victor. AU - Barnhart, Huiman. AU - Gu, Jiezhun. AU - Serrano, Jose. AU - Ahmad, Jawad. AU - Bach, Nancy. AU - Bansal, Meena. AU - Barnhart, Huiman X.. AU - Beavers, Kimberly. AU - Calvo, Francisco O.. AU - Chang, Charissa. AU - Conjeevaram, Hari. AU - Conner, Gregory. AU - Darling, Jama. AU - De Boer, Ynto. AU - Dieterich, Douglas. AU - Dipaola, Frank. AU - Durazo, Francisco A.. AU - Everhart, James E.. AU - Fontana, Robert J.. AU - Ghabril, Marwan S.. AU - Goldstein, David. AU - Gopalreddy, Vani. AU - Grewal, Priya. AU - Hayashi, Paul H.. AU - Hoofnagle, Jay. AU - Kaplowitz, Neil. AU - Liangpunsakul, Suthat. AU - Lichtman, Steven. AU - Liu, Lawrence. AU - Navarro, Victor J.. AU - ...
Gut bacteria influences drug-induced liver injury
5 Sep 2017. NUS pharmaceutical scientists found that modulation of gut bacteria could enhance drug therapeutic value.. Pharmaceutical drugs are broken down by enzymes in the liver into their metabolites, which are subsequently excreted in the faeces and urine. Drugs can also undergo chemical reactions mediated by bacteria within the gut, an important process that is commonly neglected. In a new study, a team of pharmaceutical scientists from NUS found that gut bacteria may selectively modify the breaking down of a drug. This causes certain patients to suffer from drug-induced liver injury (DILI), where there are unexpected side effects from consuming a drug, causing liver damage. The discovery and understanding of this process could potentially lead to the development of novel strategies to improve drug treatment outcomes and reduce drug-associated side effects. The study, led by Prof Eric CHAN from the Department of Pharmacy, NUS was carried out using tacrine, an anti-Alzheimers disease drug ...
Inpatient Admissions for Drug-induced Liver Injury: Results from a Single Center | SpringerLink
Objective To review all cases of drug-induced liver injury (DILI) requiring hospitalization at a single tertiary care center. Methods Patient records were identified by ICD-9 codes for inpatient visit
Drug-Induced Liver Injury EASL Guideline - EASL-The Home of Hepatology.
EASL Clinical Practice Guideline presents the available evidence on risk factors, diagnosis, management, risk minimization for Drug-Induced Liver Injury.
IJMS | Free Full-Text | Hepatotoxicity by Drugs: The Most Common Implicated Agents
Idiosyncratic drug-induced liver injury (DILI) is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov). According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab.
Use of GWAS and exome sequencing to identify genes relevant to
Use of GWAS and exome sequencing to identify genes relevant to drug-induced liver injury Ann K. Daly Institute of Cellular Medicine Newcastle University Idiosyncratic adverse drug reations Serious health problem which is expensive for society Common cause of death Loss of new drugs late in development or soon after licensing Typical incidence 1 in 10,000 to 100,000 patients exposed Local drug concentration may contribute but concentrationindependent effects important Contribution from immune system in many but not all cases Examples Drug-induced liver injury Hypersensitivity reactions and skin rash Cardiotoxicity Muscle toxicity Drug-induced toxicities associated with 28 drugs withdrawn from the US market 1976 to 2005 Range of drugs give rise to idiosyncratic DILI but due to value of drugs and rarity of problem are still used widely Wilke et al. Nature Reviews Drug Discovery 2007; 6, 904-916 Drug-induced liver injury (DILI) Rare but serious ...
Neil Kaplowitz, | Keck School of Medicine of USC
Publications. . View in: PubMed. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017 Oct; 66(4):1275-1285. View in: PubMed. The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading. Redox Biol. 2017 Sep 14; 14:164-177. View in: PubMed. Heparan sulfate promotes recovery from acute liver injury: Inhibition of progressive cell death or enhanced regeneration? Hepatology. Heparan sulfate promotes recovery from acute liver injury: Inhibition of progressive cell death or enhanced regeneration? Hepatology. 2017 Jul 18. View in: PubMed. The role of MAP2 kinases and p38 kinase in acute murine liver injury models. Cell Death Dis. 2017 Jun 29; 8(6):e2903. View in: PubMed. Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis. Int J Mol Sci. 2017 May 09; 18(5). View in: PubMed. Protective role of p53 in acetaminophen hepatotoxicity. Free Radic Biol Med. 2017 May; ...
Analysis of causality assessment methods in suspected HILI cases shows relevant gaps as assessed for accuracy, bias and...
Analysis of causality assessment methods in suspected HILI cases shows relevant gaps as assessed for accuracy, bias and transparency using data provided through the Freedom of Information Act (FOIA)
Most recent papers in the journal Clinical Drug Investigation | Read by QxMD
BACKGROUND AND OBJECTIVE: The causality assessment of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. None of the different available algorithms used for the causality assessment of DILI has been universally accepted as the gold standard. This study was conducted to examine the agreement among different causality assessment scales in reporting DILI. METHODS: The World Health Organization-Uppsala Monitoring Center (WHO-UMC), Naranjo, Roussel Uclaf Causality Assessment Method (RUCAM), Maria & Victorino (M & V) and Digestive Disease Week-Japan (DDW-J) assessment scales were used to compare the causalities in all the reported cases of DILI in our adverse drug reaction (ADR) monitoring centre from January 2014 to June 2017 ...
Hys law - Wikipedia
Hys law is a rule of thumb that a patient is at high risk of a fatal drug-induced liver injury (DILI) if given a medication that causes hepatocellular injury (not cholestatic injury) with jaundice. The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury. Some have suggested the principle be called a hypothesis or observation. Hys Law cases have three components: The drug causes hepatocellular injury, generally defined as an elevated ALT or AST by 3-fold or greater above the upper limit of normal. Often with aminotransferases much greater (5-10x) the upper limit of normal. Among subjects showing such aminotransferase elevations, they also have elevation of their serum total bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal). No other reason can be found to explain the combination of increased aminotransferase and serum total ...
Drug-Induced Liver Injury (DILI) Conference XVI | Critical Path Institute
Clinical trials in humans exposed to new drugs being developed provide data for the regulatory decisions on approval/non-approval but also provide the best information to guide optimal use postmarketing by prescribers in treating patients. Speeding and optimizing new drug development during the investigational new drug (IND) period represents the greatest opportunity to shorten time and reduce costs from discovery to approval. There is urgent need to update and revise thinking to consider investigational treatment of patients with pre-existing liver diseases such as chronic viral infection with hepatitis C or B, alcoholic and non-alcoholic steatohepatitis, and other liver disorders. It is also important to recognize hepatocyte adaptation, and to reconsider if controlled rechallenge can be done safely in the carefully controlled environment of clinical trials. This conference will seek comments and proposals from industry, investigators, and regulators on these and other controversial issues that ...
MIP-DILI | IMI Innovative Medicines Initiative
Many medicines are harmful to the liver, and drug-induced liver injury (DILI) ranks as one of the leading cause of liver failure and transplantation in western countries. However, predicting which drugs will prove toxic to the liver is extremely difficult, and often problems are not detected until a drug is already on the market. IMIs MIP-DILI project deepened the understanding of the science behind drug-induced liver injury, and improved laboratory tests which are used to predict DILI in the early stages of drug development. This is already helping pharmaceutical companies to make better decisions on which drug molecule to take forward into further research, saving time and resources, and helping ensure that only the safest and most promising drugs reach patients.
In Vitro Inhibition of the Bile Salt Export Pump Correlates with Risk of Cholestatic Drug-Induced Liver Injury in Humans | Drug...
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European Medicines Agency - Non-clinical - Non-clinical evaluation of drug-induced liver injury (DILI)
European Union agency responsible for the protection of public and animal health through the scientific evaluation and supervision of medicines.
In silicoanalysis of HLA associations with drug-induced liver injury: use of a HLA-genotyped DNA archive from healthy...
For many HLA-associated ADRs the causative allele is yet to be identified. Given the strong LD in the MHC region, it is difficult to conclude that HLA alleles that show the strongest association with drug-induced adverse reactions are indeed the causative alleles. These associations encompass a diverse range of drugs and clinical manifestations, such as DILI or delayed type hypersensitivity reactions.. The complex interplay between HLA genes and haplotypes can only be replicated in systems where these haplotypes are present. Humanized animal models, in which specific human HLA alleles can be inserted into the mouse genome, have previously been used to model autoimmunity . However, given the great complexity in the MHC region, where LD can confound the discovery of genetic associations and where there is a likely role for specific HLA haplotypes, it is unclear how successful this approach would be in studying ADRs to low molecular weight drugs in particular. Through the use of human ...
HIV infection and the liver: the importance of HCV-HIV coinfection and drug-induced liver injury
Hepatitis C virus-Human immunodeficiency virus (HCV-HIV) coinfections are identified in up to 30% of patients infected with HIV and in 8% of patients infected with HCV. Now that progression of HIV and deaths due to AIDS can be prevented by highly active antiretroviral therapy (HAART), it is clear th …
Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters...
Sigma-Aldrich offers abstracts and full-text articles by [Kathleen Köck, Brian C Ferslew, Ida Netterberg, Kyunghee Yang, Thomas J Urban, Peter W Swaan, Paul W Stewart, Kim L R Brouwer].
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury - Wellness Resources
Synthetic estrogens for regulation of menstrual cycles and hormonal replacement therapy were developed in the early 1950s and came into increasing use in thereafter. Oral contraceptives (OCCs) were approved for use in the United States in 1960 and became widely used. Initial OCCs (first generation) used somewhat high doses of estrogens (50 μg of mestranol or 20 to 50 μg of ethinyl estradiol) in combination with a progestin and had appreciable rates of estrogenic side effects. Second and third generation OCCs introduced in the 1980s and 1990s have lower doses of ethinyl estradiol (15 to 35 μg) and more modern forms of progestins (norgestrel, desogestrel and others), which have been associated with lower rates of estrogenic and other adverse side effects. Hormonal replacement therapy became increasing popular in the 1980s and 1990s. Both estrogen only and combination forms of hormonal replacement therapy were used. In women with a uterus, combination hormonal replacement therapy was recommended ...
AASLD - Topics: Drug-induced liver injury, Environmental toxins
Weiwei Shan, Christopher J. Nicol, Shinji Ito, Moses T. Bility, Mary J. Kennett, Jerrold M. Ward, Frank J. Gonzalez, Jeffrey M. ...
AASLD - Topics: Drug-induced liver injury, Specific drug effects
Victor J. Navarro, Huiman Barnhart, Herbert L. Bonkovsky, Timothy Davern, Robert J. Fontana, Lafaine Grant, K. Rajender Reddy, Leonard B. Seeff, Jose Serrano, Averell H. Sherker, Andrew Stolz, Jayant Talwalkar, Maricruz Vega, Raj ...
Enoxaparin-Induced Liver Injury: Case Report and Review of the Literature and FDA Adverse Event Reporting System (FAERS) -...
Anticoagulants are a well known cause of drug-induced liver injury (DILI). We recently encountered a 45-year-old male who developed DILI during treatment with enoxaparin, a low-molecular-weight heparin (LMWH), for dural venous thrombosis. The man received enoxaparin 80 mg subcutaneously, twice daily. After 4 days, the patient was asymptomatic but he developed liver aminotransferase elevations: AST 340 U/L and ALT 579 U/L. Investigation revealed an R ratio of 19.9 by day 5 and a Roussel Uclaf Causality Assessment Method score of 10, giving a high probable likelihood that enoxaparin was the cause of hepatic injury. Enoxaparin was discontinued on day 7, and 1 week later AST and ALT had decreased to 61 and 273 U/L, respectively. This case prompted a literature search and a review of the FDA Adverse Event Reporting System (FAERS) database for the range of hepatic adverse events (HAEs) associated with this class. A MEDLINE/PubMed search was conducted using DILI terms and cross-referenced with the
Frøydis Sved Skottvoll - Department of Chemistry
Schüller, Maria; Skottvoll, Frøydis Sved; Lundanes, Elsa & Wilson, Steven Ray Haakon (2020). Bottom-up proteomics of biomarkers to investigate drug-induced hepatotoxicity in human liver organoids as part of preclinical development. Show summary Drug-induced liver injury (DILI) is an ongoing issue in the development of drugs. It is a major cause of drug withdrawal during development, as well as being the leading cause for post-authorization withdrawal. DILI is commonly discovered in later stages of clinical trials and poses a risk to trial subjects involved in the study. European Medicines Agency (EMEA) provide guidelines for non-clinical assessment of DILI, however regulatory authorities do not require this assessment for the approval of the Investigational New Drug (IND) application for testing in human subjects. This is possibly due to lack of research and validity of current DILI practices which, at worst, could hinder promising therapeutics to enter the market. In recent years, the use of ...
DILIN's Prospective Study - Full Text View - ClinicalTrials.gov
Liver injury due to prescription and non-prescription medication use is a medical, scientific and public health problem of increasing frequency and importance in the United States. Indeed, drug-induced liver injury (DILI) is the most important reason for non-approval, withdrawal, limitation in use and clinical monitoring by the Food and Drug Administration (FDA). However, detection of signals for liver injury frequently relies upon the reporting of cases by practitioners to health authorities in post-marketing surveillance. Under-reporting of cases, lack of mandatory reporting systems, and difficulties in establishing a diagnosis make the current system sub-optimal. Moreover, with the growing use of complementary and alternative medications (CAM), there have also been increasing reports of liver toxicity due to various non-prescription herbal, dietary and food additive supplements. Because the manufacturing, dispensing and testing of these products is not regulated, the hepatotoxic potential of ...
Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk...
Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other
Your Diet Supplements Could be Ruining Your Liver
Startling new research released by the Drug-Induced Liver Injury Network reveals that your diet supplements could be making you sicker, not healthier like you had hoped. According to the data, dietary supplements account for nearly 20% of drug related liver injuries that end up in hospitals.
GastroHep News Story
A study in the most recent issue of Hepatology evaluates liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network ...
A mechanistic insight into MDMA-mediated hepatotoxicity
methylenedioxymethamphetamine (MDMA, Ecstasy) is a popular drug of abuse among young people that can induce adverse effects. However, these effects lack a specific pattern, as consumption quantities are not correlated with the initiation and severity of the injury. MDMA can cause drug-induced liver injury (DILI). Two suggested pathways that play ... read more a role in the onset of DILI are direct hepatotoxicity due to toxic metabolites and adverse immune responses. Therefore, we studied MDMA interactions with phase I and II enzymes and the possible alteration of immune events in several in vitro systems (human liver (THLE) cells transfected with individual CYP450, rat liver microsomes, human PXR-mediated CYP3A4-reporter gene assay, rat primary hepatocytes, HepG2, THP-1 and PBMC). Our data suggests that not only CYP2D6 but also CYP3A4 plays an important role in MDMA bioactivation. Furthermore,MDMA alone or in combination with other therapeutic drugs inhibited CYP3A catalytic activity. This ...
As reported previously (Zou et al., 2009), SLD/LPS cotreatment induced severe liver injury in rats. Proinflammatory cytokines, especially TNF-α, have proved to play a critical role in other drug/LPS-induced liver injury models (Shaw et al., 2007; Tukov et al., 2007). Moreover, studies suggest that reactive drug metabolites produced in liver are critical for idiosyncratic hepatotoxicity from some drugs (Kaplowitz, 2005). Therefore, we focused in this study on the roles of TNF-α and the toxic metabolite of SLD and their interaction in SLD/LPS-induced liver injury.. The concentration of TNF-α in serum was elevated in rats after exposure to LPS, and SLD significantly enhanced the LPS-mediated increase in TNF-α as early as 1 h. Besides SLD, other drugs associated with idiosyncratic hepatotoxicity in humans, such as ranitidine and trovafloxacin, also had a synergistic effect on the LPS-mediated increase in TNF-α in rodents (Shaw et al., 2007; Tukov et al., 2007). Sulindac and other NSAIDs ...
Drug-induced hepatitis is a redness and swelling (inflammation) of the liver that is caused by a harmful (toxic) amount of certain medicines.
contest dataset [Camda 2013]
Question 2: Can we predict the liver injury in humans using toxicogenomics data from animals. Around 40% of drug-induced liver injury (DILI) cases are not detected in the preclinical studies using the conventional indicators (such as pathology, clinical chemistry data). It has been hypothesized that genomic biomarkers will be more sensitive than conventional markers in detecting human hepatotoxicity signals in preclinical studies (i.e., in vitro and in vivo assays). In this project, we provide the human hepatotoxicity data for most of the drugs (the last three columns in the table named Drug Information). The contests can explore the possibility of predicting the DILI potential in humans using the in vitro data from rat primary hepatocytes or human primary hepatocytes, or the animal data from two different treatment protocols. Alternatively, these data can also be combined to enhance the predictive power for the human hepatotoxic potential ...
Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds that cause idiosyncratic hepatotoxicity. In the current study, we applied machine learning, a Bayesian modeling method with extended connectivity fingerprints and other interpretable descriptors. The model that was developed and internally validated (using a training set of 295 compounds) was then applied to a large test set relative to the training set (237 compounds) for external validation. The resulting concordance of 60%, sensitivity of 56%, and specificity of 67% were comparable to results for internal validation. The Bayesian model with extended connectivity functional class fingerprints of maximum diameter 6 (ECFC_6) and interpretable descriptors suggested several substructures that are chemically reactive and may also be ...
Hepatotoxicity: From Genomics to In Vitro and In Vivo Models | Toxicology | Pharmaceutical & Medicinal Chemistry | Chemistry |...
Contributors. Preface.. Acknowledgements.. SECTION 1: MODELS FOR HEPATOTOXICITY TESTING.. 1 Current in vitro Models to Study Drug-Induced Liver Injury (Julio C. Davila, Jinghai J. Xu, Keith A. Hoffmaster, Peter J. OBrien and Stephen C. Storm).. 2 Utilization of an in vitro Hepatotoxicity Test in the Early Stage of Drug Discovery (Ikuo Horii, Hiroshi Yamada, Rie Kikkawa, Toshinori Yamamoto, Tamio Fukushima and Kaori Tomizawa).. 3 Use of Hepatocytes for Characterizing a Candidate Drugs Metabolism and Drug Interaction Potential (Srikanth C. Nallani, John M. Strong and Shiew Mei Huang).. 4 Human-Based in vitro Experimental Systems for the Evaluation of Human Drug Safety (Albert P. Li).. 5 Hepatocytes as a Model for Screening Food-Related Hepatotoxins and Studying Mechanisms of their Toxicity (Saura C. Sahu).. 6 Some Experimental Models of Liver Damage (Pablo Muriel).. SECTION 2: HEPATOCYTE CULTURES.. 7 Application of Short- and Long-Term Hepatocyte Cultures to Predict Toxicities (Gregor Tuschl, ...
Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study | BMC Medicine | Full Text
Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin | 2 × ULN. DILI was identified in 58 of
PPT - Liver Injury linked to Flavocoxid PowerPoint Presentation - ID:1283082
Flavocoxid, a natural solution used to cure arthritis, may have been responsible for serious liver injury in four patients doing research of drug-induced liver injury, according to the discoveries of US research. Slideshow 1283082 by OMICSPublishingGroup
FDA analysis shows body-building products labeled to contain steroid and steroid-like substances continue to inflict serious...
FDAs review of adverse event reports supports a relationship between the use of various body-building products suspected to contain steroids and serious liver injury requiring hospitalization. A majority of the cases involved elevated liver enzymes (i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AlkP)), which are indicators of liver injury. In some cases, consumers were taking multiple body-building products, which precludes the ability to limit the findings to a specific product or ingredient and raises the concern that the harmful effects may be caused by an interaction between the two products.. Drug-induced liver injury (DILI) is a known possible harmful effect of using anabolic steroid-containing products. In addition, anabolic steroids (or AAS) may cause other serious adverse effects such as abnormal fat and cholesterol in the blood, mood disorders, androgenic effects (acnes, baldness, excessive hair growth in females), gonadal ...
Operative Techniques for Severe Liver Injury
www.MOLUNA.de Operative Techniques for Severe Liver Injury  - Chapter 1 Surgical Anatomy of the LivernThomas M. Scalea & Brandon BrunsnnChapter 2 Treatment of Liver Injuries: An OverviewnCharles E. Lucas & Anna M. LedgerwoodnnChapter 3 Resuscitation Maneuvers for ExtremisnThomas M. ScaleannChapter 4 Massive Hepatic Hemorrhage: IdentificationnAdrian W. Ong, Vicente Cortes, & Aurelio RodrigueznnChapter 5 Massive Hepatic Hemorrhage: Initial Steps
A Critical Role for IFN Regulatory Factor 1 in NKT Cell-Mediated Liver Injury Induced by α-Galactosylceramide | The Journal of...
The liver has been well recognized not only as an important metabolic organ, but also as an important site for immune responses. It is widely accepted that immune-mediated liver injury plays a central role in the pathophysiology of many liver diseases (36, 37). The remarkable enrichment of NKT cells in mouse liver has attracted much research attention to explore the role of this unique cell population in the pathogenesis of hepatic diseases, and increasing evidence has suggested that NKT cells are indeed involved in the development of many liver diseases (14). Activation of NKT cells with α-GalCer causes moderate liver injury, which has been recognized as a useful model to investigate immune-mediated liver injury (14, 17-19). The major and novel findings of this study are: 1) α-GalCer injection causes a remarkable increase in IRF-1 expression in mouse liver; 2) α-GalCer-induced IRF-1 upregulation in vivo is TNF-α- and IFN-γ-dependent; 3) IRF-1 plays an important role in mediating ...
BSEP - Transporters - Solvo Biotechnology
Gene name: ATP binding cassette subfamily B, member 11 (ABCB11). Summary. ABCB11, more commonly referred to as BSEP (Bile Salt Export Pump) is a uni-directional, ATP-dependent efflux transporter that plays an important role in the elimination of bile salts from the hepatocyte into the bile canaliculi for export into the gastrointestinal tract (GIT). It is almost exclusively expressed in the liver, with much lower levels reported in the kidney. It is predominantly of relevance to hepatotoxicity, as BSEP inhibition by a drug and/or its metabolites can result in the build-up of bile salts in the liver, which can lead to cholestasis and drug-induced liver injury (DILI). Compared to other drug transporters there are only few identified drug substrates and inhibitors of BSEP; thus, its involvement in drug-drug interactions (DDI) is very limited. The relevance of in vitro BSEP inhibition as a predictor of clinical outcomes is not clearly established, but whenever cholestatic liver injury is observed in ...
SOLU-MEDROL - Renal and Urology News
Not for epidural use; serious neurologic events may occur. Cerebral malaria, optic neuritis: not recommended. Latent or active amebiasis. Strongyloides infestation. Ocular herpes simplex. Cirrhosis. Tuberculosis. If exposed to chickenpox or measles, consider prophylactic passive immune therapy. Ulcerative colitis if perforation pending. Peptic ulcer. Diverticulitis. Intestinal anastomoses. Myasthenia gravis. Systemic sclerosis. Recent MI. CHF. Hypertension. Renal insufficiency. Osteoporosis. Diabetes. Hypothyroidism. Kaposis sarcoma. Supplement with additional steroids in physiologic stress. May increase risk and mask signs of infection. May cause electrolyte imbalances, adrenocortical insufficiency, psychotic derangements. Alternate, intermittent, or single-daily doses at 8 AM minimize adrenal suppression. Monitor weight, growth, fluid and electrolyte balance. IV: drug-induced liver injury; discontinue if toxic hepatitis occurs. Intrasynovial: avoid previously infected or unstable joints. ...
How to interpret liver function tests
The liver enzymes are in two main groups - ALP and GGT, produced predominantly by the bile ducts; and ALT and AST, produced predominantly by hepatocytes. Liver enzymes are a poor reflector of liver function, but rather of cholestasis and liver cell integrity, respectively .. Liver enzymes have different normal ranges, so assessment of their relative abnormalities by number of times greater than their upper limit of normal (ULN) can be more informative than the absolute values.. When ALP is raised more times its ULN than either ALT or AST, this suggests a cholestatic pattern indicating biliary pathology. In the acute setting, a cholestatic pattern of LFTs is seen with bile stones, when accompanied by colicky right upper quadrant pain or in cholestatic drug-induced liver injury when there is a history of a new causative medication. A more chronic presentation may be due to pancreatic, liver or bile duct tumours or cholestatic autoimmune liver disease such as primary biliary cholangitis or ...
Toxin induced liver disease. Drug induced liver disease. Drug induced liver damage. Drug induced liver injury. Hepatogenous ... Toxin induced hepatitis. Drug induced hepatitis. Drug-induced hepatic necrosis. Drug induced hepatic fibrosis. Drug induced ... Patterns of injury. Patterns of drug-induced liver disease Type of injury:. Hepatocellular. Cholestatic. Mixed ... Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures. ...
a b "Omeprazole and Esomeprazole". Clinical and Research Information on Drug-induced Liver Injury. National Institutes of ... a b "Lansoprazole, Dexlansoprazole". Clinical and Research Information on Drug-induced Liver Injury. National Institutes of ... "Pantoprazole". Clinical and Research Information on Drug-induced Liver Injury. National Institutes of Health. Retrieved May 8, ... "Rabeprazole". Clinical and Research Information on Drug-induced Liver Injury. National Institutes of Health. Retrieved May 8, ...
Mechanisms of drug-induced liver injury: from bedside to bench. Nat Rev Gastroenterol Hepatol. 2011 Apr;8(4):202-11. Review. ... In a 1993 clinical study at the NIH, unexpected toxicity led to the death of 5 out of 15 patients from liver failure associated ... It is suspected that the drug's toxicity was due to its damaging mitochondria. Tujios S, Fontana RJ. ... with lactic acidosis; two further participants required liver transplantation. This toxicity was unusual in that it was not ...
Kaniwa N, Saito Y (June 2013). "Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury". Journal ... Moody D (2004). "Drug interactions with benzodiazepines". In Raymon LP, Mozayani A (eds.). Handbook of Drug Interactions: a ... Schlatter J, Madras JL, Saulnier JL, Poujade F (September 1999). "[Drug interactions with methadone]" [Drug interactions with ... As a drug that induces cytochrome P450 enzymes, it accelerates elimination of many benzodiazepines and decreases their action.[ ...
Kaniwa N, Saito Y (June 2013). "Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury". Journal ... Moody D (2004). "Drug interactions with benzodiazepines". In Raymon LP, Mozayani A (eds.). Handbook of Drug Interactions: a ... drugs.com drugs.com international listings for carbamazepine Archived 2015-06-19 at the Wayback Machine Page accessed June 3, ... Schlatter J, Madras JL, Saulnier JL, Poujade F (September 1999). "[Drug interactions with methadone]" [Drug interactions with ...
Drug-Induced Liver Disease. pp. 605-619. doi:10.1016/B978-0-12-387817-5.00033-9. ISBN 9780123878175. PMID 11096606. Liver ... In rare instances, clinically apparent acute liver injury has occurred during nilutamide therapy, but the number of published ... "Drug-induced gynecomastia: an evidence-based review". Expert Opinion on Drug Safety. 11 (5): 779-795. doi:10.1517/14740338.2012 ... Phillipe Camus; Edward C Rosenow III (29 October 2010). Drug-induced and Iatrogenic Respiratory Disease. CRC Press. pp. 235-. ...
Andrade, Raúl J; Robles, Mercedes; Ulzurrun, Eugenia; Lucena, M Isabel (2009). "Drug-induced liver injury: insights from ... "Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease". Liver International. 34 (7): e171-e179. ... In the case of overdoses, the storage of GSH will not be enough for NAPQI detoxication, thereby resulting in acute liver injury ... Hepatotoxicity indicates the drug's toxicity to liver. Paracetamol (acetaminophen, APAP) is converted into the hepatotoxic ...
In early 2020 a single case report of drug-induced liver injury following use of RAD 140 was published. RAD 140 is still in the ... Flores, Joan Ericka; Chitturi, Shivakumar; Walker, Sarah (2020). "Drug‐Induced Liver Injury by Selective Androgenic Receptor ...
"Nizatidine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf. 25 January 2018. PMID ... "Nizatidine: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 20 March 2020. Fischer J, Ganellin CR (2006 ... "Nizatidine". Drug Information Portal. U.S. National Library of Medicine. Medicine portal. ... Food and Drug Administration (FDA). However, a year later, they sold rights of the Axid Oral Solution (including the issued ...
"Drug Record - Amoxicillin-Clavulanate". LiverTox - Clinical and Research Information on Drug-Induced Liver Injury. Retrieved ... Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as ... After several attempts, Beecham finally filed for US patent protection for the drug in 1981, and U.S. Patents 4,525,352, ... Clavulanic acid was discovered around 1974-75 by British scientists working at the drug company Beecham from the bacteria ...
"Green Tea". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institutes of Health. Green tea ... and Outcomes From a Prospective Study of Drug-Induced Liver Injury in the United States". Gastroenterology. 135 (6): 1924-1934 ... ingestion of large amounts of green tea have been implicated in cases of clinically apparent acute liver injury, including ... Consumption of green tea extract is linked to hepatotoxicity and liver failure. Green tea leaves are initially processed by ...
"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury". National Institute of Diabetes and Digestive and ... ISBN 978-1-4614-1399-8. Greenwood D (2008). "4. Wonder Drugs". Antimicrobial Drugs: Chronicle of a Twentieth Century Medical ... Other side effects may include muscle or joint pains, shortness of breath, and liver problems. It appears to be safe during ... Table of Selected Analogue Classes". In Fischer J, Ganellin CR (eds.). Analogue-based Drug Discovery. Wiley-VCH. p. 491. ISBN ...
List of herbs with known adverse effects
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and ... Cupp, M. J. (1999). "Herbal remedies: Adverse effects and drug interactions". American Family Physician. 59 (5): 1239-1245. ... either alone or in interaction with other herbs or drugs. Non-inclusion of an herb in this list does not imply that it is free ... "Hepatotoxicity Induced by 'the 3Ks': Kava, Kratom and Khat". International Journal of Molecular Sciences. 17 (4): 580. doi: ...
"Pexidartinib". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of ... "Drug Approval Package: Turalio". U.S. Food and Drug Administration (FDA). 22 July 2019. Retrieved 17 March 2020. "New Drug ... "Microglial Magic: Drug Wipes Them Out, New Set Appears". Alzforum. 18 April 2014. Retrieved 19 March 2020. "Drug Trials ... The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. The approval of pexidartinib was ...
"Methocarbamol". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and ... Although unlikely, it is impossible to rule out that methocarbamol may cause mild liver injury with use. Skeletal muscle ... ISBN 978-1-4612-2124-1. "Methocarbamol". Drugs.com. Retrieved 12 May 2018. "New Drugs and Indications Reviewed at the May 2003 ... "Methocarbamol - Drug Usage Statistics". ClinCalc. Retrieved 18 February 2021. Chou, Roger; Peterson, Kim; Helfand, Mark (August ...
"Imipenem-Cilastatin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf. 17 January 2017 ... Common adverse drug reactions are nausea and vomiting. People who are allergic to penicillin and other β-lactam antibiotics ... Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, ... Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 497. ISBN 9783527607495. Kahan FM, Kropp H ...
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of ... Common adverse drug reactions (ADRs) associated with the use of dicloxacillin include: diarrhoea, nausea, rash, urticaria, pain ... Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 491. ISBN 9783527607495. Dicloxacillin. ... Adelaide: Australian Medicines Handbook; 2006 "Dicloxacillin". MedlinePlus Drug Information. U.S. National Library of Medicine ...
"Cat's claw: Clinical and research information on drug-induced liver injury". LiverTox, US National Institute of Diabetes and ... "Cat's claw". Drugs.com. 7 June 2018. Retrieved 11 January 2019. "Assessment report on Uncaria tomentosa (Willd. ex Schult.) DC ... Phytochemicals in cat's claw may inhibit the liver enzyme, CYP3A4, which oxidizes organic compounds, and may interfere with the ... intended effect of prescription drugs. List of ineffective cancer treatments "Uncaria tomentosa". Germplasm Resources ...
"Niacin". IN: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet). Bethesda, MD: National ... both biomarkers of liver injury. The increases usually resolves even when drug intake is continued. However, less commonly, the ... In rare instances the injury is severe, and progresses to liver failure. The high doses of niacin used to treat hyperlipidemia ... Laropiprant is a prostaglandin D2 binding drug shown to reduce niacin-induced vasodilation and flushing side effects. A ...
Kelava T, Cavar I, Čulo F (Oct 2010). "Influence of small doses of various drug vehicles on acetaminophen-induced liver injury ... induced liver injury in mice. In addition to the above, DMSO is finding increased use in manufacturing processes to produce ... DMSO is also used to dissolve test compounds in in vitro drug discovery and drug design screening programs (including high- ... In Australia, it is listed as a Schedule 4 (S4) Drug, and a company has been prosecuted for adding it to products as a ...
Iorga, Andrea; Dara, Lily; Kaplowitz, Neil (2017-05-09). "Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, ... However, the exact mechanism of how the binding of iproniazid derivatives to liver proteins would induce liver necrosis remains ... "Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism". The Journal of Pharmacology and Experimental Therapeutics ... it was replaced by medicinal xenobiotics that are less harmful to the liver. Examples of antidepressant drugs that are nowadays ...
"Performance of preclinical models in predicting drug-induced liver injury in humans: a systematic review". Scientific Reports. ... or biological agents on living organisms and the environment, including the prevention and amelioration of such effects. EBT ...
December 2006). "Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry". ... nausea and drug-induced lymphocytic colitis has been associated with bentazepam. Severe liver damage and hepatitis has also ... July 2000). "Chronic liver injury related to use of bentazepam: an unusual instance of benzodiazepine hepatotoxicity". ... Whilst liver failure from bentazepam is considered to be rare, liver function monitoring has been recommended for all patients ...
Side effects of bicalutamide
"A case of asymptomatic primary biliary cholangitis accompanied by drug-induced liver injury caused by bicalutamide". Journal of ... "Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug ... Drug-Induced Liver Disease. CRC Press. pp. 618-. ISBN 978-0-203-90912-6. Kim JH, Yoo BW, Yang WJ (May 2014). "Hepatic failure ... appears to be an important risk factor for drug-induced hepatotoxicity. As such, the risk of liver changes with bicalutamide ...
"Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury", ... and nR criteria to predict acute liver failure or transplantation in patients with drug-induced liver injury.", ... Hy's law is a rule of thumb that a patient is at high risk of a fatal drug-induced liver injury (DILI) if given a medication ... The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury. Some have suggested the ...
2011). "Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb". ... "Polygonum multiflorum and liver reactions". MHRA. 2006. Archived from the original on 2014-12-05. "He-shou-wu (Polygonum ... Caution must be taken, however, as overconsumption can lead to toxicity-induced hepatitis. More than 100 chemical compounds ... Gut and Liver. 5 (4): 493-9. doi:10.5009/gnl.2011.5.4.493. PMC 3240794. PMID 22195249. Tang, J (2007). "Antioxidant activity of ...
Analysis of genetic polymorphisms of UGT2B7 in anti-tuberculosis drug-induced liver injury (ATLI) found no association between ... that can cause serious drug-induced liver injury, showed that mutant UGT2B7 with the C802T SNP had a 6-fold lower clearance of ... "Association of UGT2B7 polymorphisms with risk of induced liver injury by anti-tuberculosis drugs in Chinese Han". International ... "Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer". ...
Type 2 diabetes
"Drug-induced diabetes mellitus". Expert Opinion on Drug Safety. 4 (6): 1097-109. doi:10.1517/14740322.214.171.1247. PMID 16255667. ... and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of ... liver, and fat tissue. In the liver, insulin normally suppresses glucose release. However, in the setting of insulin ... Krentz AJ, Bailey CJ (February 2005). "Oral antidiabetic agents: current role in type 2 diabetes mellitus". Drugs. 65 (3): 385- ...
De Smet, Peter A.G.M. (December 1997). "The Role of Plant-Derived Drugs and Herbal Medicines in Healthcare". Drugs. 54 (6): 801 ... Such disease-inducing imbalances can be adjusted and balanced using traditional herbs, minerals and heavy metals. Ayurveda ... who are encouraged not only to pay their last penny but to be treated with something that shortens their lives. "At the same ... "have occurred when faith healing was elected instead of medical care for serious injuries or illnesses". A 2001 double- ...
Other syndromes or conditions which can induce skeletal muscle atrophy are liver disease, and starvation. Muscle atrophy occurs ... when the patient has a primary injury such as an immobilized broken bone (set in a cast or immobilized in traction), for ... A novel class of drugs, called SARM (selective androgen receptor modulators) are being investigated with promising results. ... Therefore, one way in which not exercise induces an increase in muscle mass is to down regulate the pathways which have the ...
By c. 45,000 BP, humans lived at 61°N latitude in Europe. By c. 30,000 BP, Japan was reached, and by c. 27,000 BP humans ... As with modern hunter-gatherer societies, music may have been used in ritual or to help induce trances. In particular, it ... Thus, a thrown hand axe would not usually have penetrated deeply enough to cause very serious injuries. Nevertheless, it could ... By the end of the Lower Paleolithic, members of the hominin family were living in what is now China, western Indonesia, and, in ...
... and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of ... "Drug Trials Snapshots: Aklief". U.S. Food and Drug Administration (FDA). 11 October 2019. Archived from the original on 19 ... Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A (March 2017). "Flutamide-induced hepatotoxicity: ... Aslam I, Fleischer A, Feldman S (March 2015). "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs. 20 ...
Hematopoietic stem cell transplantation
Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid ... Drug risks. Filgrastim is typically dosed in the 10 microgram/kg level for 4-5 days during the harvesting of stem cells. ... G-CSF has also been described to induce genetic changes in mononuclear cells of normal donors. There is evidence that ... The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens ...
Abortion - Simple English Wikipedia, the free encyclopedia
These induced abortions have more complications than abortions done by doctors.. Women who live in places where abortion is ... They were also more likely to have problems with alcohol and illegal drugs than those women who did not have an abortion. The ... which puts those women in danger of death or injury. Pro-choice people believe the way to prevent abortion is to make sure ... In places where induced abortions are legal less than 1% of induced abortions have a bad complication. If doctors do induced ...
Occupational health psychology
Employees must balance their working lives with their home lives. Work-family conflict is a situation in which the demands of ... 2004). 1992-2001 Census of fatal occupational injuries (CFOI) Revised data. Washington, DC: U.S. Department of Labor, Bureau of ... Chronic solvent-induced encephalopathy (CSE). *Coalworker's pneumoconiosis ("black lung"). *Concussions in sport ... Kidd, P., Scharf, T., & Veazie, M. (1996). Linking stress and injury in the farming environment: A secondary analysis. Health ...
"Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury". The Journal of Clinical ... Recombinant alpha-1 antitrypsin is not yet available for use as a drug but is under investigation as a therapy for alpha-1 ... A liver biopsy will show abundant PAS-positive globules within periportal hepatocytes. The protein was initially named " ... Normally, A1AT leaves its site of origin, the liver, and joins the systemic circulation; defective A1AT can fail to do so, ...
In species that live near the poles, the blubber can be as thick as 11 inches. This blubber can help with buoyancy (which is ... Mass strandings have been triggered by sonar activity, resulting in injury or death. ... he was told by the Great Spirit where to find special mushrooms that would give him the strength to drag the whale back to the ... "Quantifying the sensitivity of Arctic marine mammals to climate-induced habitat change" (PDF). Ecological Applications. 18 (2 ...
ادرار کردن - ویکیپدیا، دانشنامهٔ آزاد
1.3.2 Experimentally induced disorders *126.96.36.199 Deafferentation. *188.8.131.52 Denervation. *184.108.40.206 Spinal cord injury ... Coren, Stanley (5 January 2006). The Intelligence of Dogs: A Guide to the Thoughts, Emotions, and Inner Lives of Our Canine ... A drug that increases urination is called a diuretic, whereas antidiuretics decrease the production of urine by the kidneys. ... Experimentally induced disorders. This section does not cite any sources. Please help improve this section by adding citations ...
... and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of ... corticosteroid-induced; and 4) a heterogonous mechanism associated with structural change and chronic inflammation. In ... become blind from incorrect diagnosis and from ineffectual prescription of drugs, antibiotics or steroids. In addition, ... Eye injuries, most often occurring in people under 30, are the leading cause of monocular blindness (vision loss in one eye) ...
多囊卵巢綜合症 - 维基百科，自由的百
Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the ... Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ... Rasgon N. The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence. J Clin ... Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome. New England Journal of ...
a b Salo, P., Nordström, M., Thomson, R. L., & Korpimäki, E. (2008). Risk induced by a native top predator reduces alien mink ... Four Baikal seal (Pusa sibirica) pups were taken in Lake Baikal. They are considered a predator even for live grey seal ( ... Petrified by the darkness once drug below, white-tailed eagles apparently offer no resistance once caught. However, habitat had ... The white-tailed eagles must then attack birds at times of vulnerability or injury, or will often utilize the prey's escape ...
Surviving Sepsis Campaign
Induced coma. *Mechanical ventilation. *Therapeutic hypothermia. *Total parenteral nutrition. *Tracheal intubation. Drugs. * ... Acute liver failure. Respiratory failure. Multiple organ dysfunction syndrome. *Neonatal infection. *Polytrauma ...
Chronic obstructive pulmonary disease
... and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of ... Aspirin-induced. Exercise-induced. Bronchiectasis. Cystic fibrosis. unspecified. Bronchitis. Bronchiolitis Bronchiolitis ... "Fluoroquinolone Antibacterial Drugs: Drug Safety Communication - FDA Advises Restricting Use for Certain Uncomplicated ... People who live in large cities have a higher rate of COPD compared to people who live in rural areas. While urban air ...
Radiation-induced lung injury. *Microwave burn. *Injury from toxin or as adverse effect of a pharmaceutical drug *Toxic injury ... Liver injury. *Head injury *Penetrating head injury. *Closed head injury. *Musculoskeletal injury *Articular cartilage injuries ... Injury from internal causes such as reperfusion injury. By locationEdit. *Wound, an injury in which skin is torn, cut or ... Illness and injuries during spaceflight. Injury severity scoreEdit. The injury severity score (ISS) is a medical score to ...
Hall JD (1982). "Repair of psoralen-induced crosslinks in cells multiply infected with SV40". Mol. Gen. Genet. 188 (1): 135-8. ... Water solubility is important for two reasons: pharmacokinetics relating to drug solubility in blood and necessitating the use ... an unusual cause of extensive burn injury". Burns. 22 (8): 633-5. doi:10.1016/S0305-4179(96)00028-9. PMID 8982544.. ... "RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure". Cell. 165 (5): 1267-1279. doi:10.1016/j.cell. ...
ICD-10 Chapter V: Mental and behavioural disorders
Substance intoxication / Drug overdose. *Withdrawal. *Substance-induced psychosis. *SUD *Substance abuse / Substance use ... Injury, poisoning and certain other consequences of external causes XX V01-Y98 External causes of morbidity and mortality ... F19) multiple drug use and use of other psychoactive substances (F20-F29) Schizophrenia, schizotypal and delusional disorders[ ... Benzodiazepine drug misuse Benzodiazepine dependence Benzodiazepine withdrawal syndrome (F14) use of cocaine Cocaine ...
Brain-derived neurotrophic factor
BDNF is a regulator of drug addiction and psychological dependence. Animals chronically exposed to drugs of abuse show ... "Alzforum: Live Discussions. Alzheimer Research Forum. Archived from the original on 11 October 2008. Retrieved 21 August 2008. ... Research has reported that the interaction between BDNF and TrkB (the receptor to BDNF) is highly important in inducing ... a widely expressed activity-dependent neurotic factor that regulates plasticity and is unregulated following hypoxic injury. ...
During the same period, numerous experimental drugs have been shown to be neuroprotective in animal models of brain injury. ... and synapses are also subjected to TBI-induced damage [18,19]. Similarly, not only are neurons at risk for injury, but also ... A biomarker can be any kind of molecule indicating the existence, past or present, of living organisms. In the fields of ... dendritic injury, neuronal cell body injury, demyelination, synaptic injury and astroglia injury, and microglia responses. ...
... coupled with the high cost of defending personal-injury lawsuits brought by some people who took the drug. Generic ... Inhibition of hippocampal neurogenesis may also play a role in the development of isotretinoin-induced depression. A ... Liver. Elimination half-life. 10-20 hours. Excretion. Kidney and fecal. Identifiers. ... Isotretinoin is the only non-psychiatric drug on the FDA's top 10 list of drugs associated with depression and is also ...
Hence, high levels of free radicals can cause damage to them and induce dysraphic anomalies (neural tube defects).[citation ... Thus, SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. One exception is Lactobacillus ... Marberger H, Huber W, Bartsch G, Schulte T, Swoboda P (1974). "Orgotein: a new anti-inflammatory metalloprotein drug evaluation ... though they are more sensitive to hyperoxic injury. Knockout mice of any SOD enzyme are more sensitive to the lethal ...
For over-18- to 20-year-olds living at home this increases to A$110.15 per week. For those aged 18-20 not living at home the ... One common criticism of unemployment insurance is that it induces moral hazard, the fact that unemployment insurance lowers on- ... aural care and subsidised prescription drugs carrying a €2.50 per item charge to a maximum monthly contribution of €25 per ... Occupational injury. *Occupational stress. *Repetitive strain injury. *Sick building syndrome. *Work accident *Occupational ...
List of countries with universal health care
Olsen, Sonja K.; Brown, Robert S. (2008). "Live Donor Liver Transplantation: Current Status". Current Gastroenterology Reports ... Some essential drugs are offered free of charge in these hospitals. An outpatient card at AIIMS costs a one-time fee of 10 ... Obvious unexpected emergencies like accidental injuries or sudden illness are customarily covered, but those that could be ... a move expected to reduce medically induced bankruptcy. As of October 7, 2016, the U.S. uninsured rate fell to 10.9% from the ...
Amyotrophic lateral sclerosis
Drugs tested and not shown to be effective in clinical trials in humans include antiviral drugs, anti-excitotoxic drugs, growth ... Head injury. A 2015 review found that moderate to severe traumatic brain injury is a risk factor for ALS, but whether ... of people with ALS live between five and 10 years after symptoms begin. Guitarist Jason Becker has lived since 1989 with the ... The zebrafish has transparent embryos that can be injected with DNA or RNA and has a lifespan of up to two years. Induced ...
5-fold increase in drug-induced mental disorders, 2-fold increase in disorders such as schizophrenia, 2 to 3-fold increase in ... 69.2 years for those living in the Northern Territory to a high of 75.0 years for those living in New South Wales.[ ... "The burden of disease and injury in Aboriginal and Torres Strait Islander peoples: Summary report". Brisbane: School of ... 2007 National Drug Strategy Household Survey: detailed findings. Drug statistics series no. 22. Cat. no. PHE 107. Canberra: ...
Mold health issues
... induce liver cancer. Mycotoxin-contaminated grain and other food products have a significant impact on human and animal ... Today, the US Food and Drug Administration and the agriculture industry closely monitor mold and mycotoxin levels in grains and ... in a toxic mold-related personal injury lawsuit against the owners and managers of their apartment in Sacramento, California.[ ... Mold-induced hypersensitivityEdit. The most common form of hypersensitivity is caused by the direct exposure to inhaled mold ...
Vaping-associated pulmonary injury. *War on Drugs. *Cannabinoid hyperemesis syndrome (CHS). *List of investigational analgesics ... THC is highly lipophilic and initially taken up by tissues that are highly perfused, such as the lung, heart, brain, and liver. ... Based on a single study, oral CBD extract was rated probably ineffective in treating levodopa-induced dyskinesia in Parkinson's ... "The UN Drug Control Conventions". 8 October 2015.. *^ "Drug Schedules; Schedule 1". US Drug Enforcement Administration, ...
a b c U.S. Food and Drug Administration: "Listing of Food Additives Status Part I". Archived from the original on January 17, ... Recent orders of birds and most mammals make ascorbic acid in their liver. A number of species of passerine birds also do ... These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with ... Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury". Nutrition and Metabolic ...
Drug-induced liver injury: MedlinePlus Medical Encyclopedia
... is an injury of the liver that may occur when you take certain medicines. ... Drug-induced liver injury (DILI) is an injury of the liver that may occur when you take certain medicines. ... Drug-induced liver injury most often goes away within days or weeks after you stop taking the drug that caused it. ... You have been diagnosed with drug-induced liver injury and your symptoms do not get better after you stop taking the medicine. ...
Drug-Induced Liver Injury Is On The Rise - Redorbit
"Drug-induced liver injury is not a single, uncommon disease of the general population, but rather a series of rare diseases ... The study also showed that drug-induced liver injury was caused by a single prescription medication in 75 percent of cases, by ... More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in ... Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 ...
Causality Assessment Methods in Drug-Induced Liver Injury | SpringerLink
... and herb-induced liver injury (HILI) but is also critical for the... ... is not only indispensable for the diagnosis of suspected drug-induced liver injury (DILI) ... Drug-Induced Liver Injury Network (DILIN) (2010) Important elements for the diagnosis of drug-induced liver injury. Clin ... is not only indispensable for the diagnosis of suspected drug-induced liver injury (DILI) and herb-induced liver injury (HILI) ...
Gene Variant Flags Risk for Drug-Induced Liver Injury in MS
Researchers discovered a genetic difference that could identify people with multiple sclerosis at risk for drug-induced liver ... patients with MS positive for the rs2205986 variant had more than an eightfold greater likelihood of drug-induced liver injury ... Genome-wide testing revealed three regions associated with interferon-β-induced liver injury. The strongest association was ... "We propose it would be liver cells that contain the liver injury marker, ALT, that are dying in the presence of interferon-β," ...
Bile Salt Export Pump: Drug-Induced Liver Injury and Assessment Approaches | SpringerLink
Drug-Induced Liver Injury and Assessment Approaches. In: Chen M., Will Y. (eds) Drug-Induced Liver Toxicity. Methods in ... Bile salt export pump BSEP Cholestasis Drug-induced liver injury DILI Drug-induced cholestasis BSEP activity BSEP transcription ... Abboud G, Kaplowitz N (2007) Drug-induced liver injury. Drug Saf 30:277-294PubMedPubMedCentralCrossRefGoogle Scholar ... Sarges P, Steinberg JM, Lewis JH (2016) Drug-induced liver injury: highlights from a review of the 2015 literature. Drug Saf 39 ...
Acetaminophen Leading Culprit in Drug-Induced Liver Injury | Medpage Today
RIDGEWOOD, N.J. -- Acetaminophen leads the list of drugs implicated in liver damage requiring transplantation, along with ... Source Reference: Hayashi P, Watkins P "Progress in our understanding of severe drug-induced liver injury" Liver Transpl 2009; ... But caution them that young people taking antiepileptic drugs who develop drug-induced liver injury have a higher likelihood of ... Liver Transplantation. Source Reference: Mindikoglu A, et al "Outcome of liver transplantation for drug-induced acute liver ...
Drug-Induced Liver Injury: An Overview
Drug-induced liver injury. UptoDate. www.uptodate.com/contents/drug-induced-liver-injury. Accessed July 8, 2016.. 6. Pandit A, ... Drug-induced liver injury in obesity. J Hepatol. 2013;58:824-826.. 25. Corsini A, Bortolini M. Drug-induced liver injury: the ... Drug-induced liver injury. Mayo Clin Proc. 2014;89:95-106.. 50. Singh D, Cho WC, Upadhyay G. Drug-induced liver toxicity and ... Mechanisms of drug-induced liver injury. AAPS J. 2006;8:e48-e54.. 9. Yuan L, Kaplowitz N. Mechanisms of drug-induced injury. ...
Studies Document Some Severe Outcomes After Drug-induced Liver Injury | NIDDK
... for the United States Drug Induced Liver Injury Network. Idiosyncratic drug induced liver injury in African-Americans is ... Drug-induced liver injury is a relatively rare, but potentially life-threatening type of liver disease that is a growing cause ... Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology 66: 1275-1285, doi: 10.1002/ ... In the Networks study, the most frequent cause of drug-induced liver injury in African Americans was a two-drug antibiotic ...
Drug-Induced Liver Injury | Washington Manual of Medical Therapeutics
Drug-Induced Liver Injury answers are found in the Washington Manual of Medical Therapeutics powered by Unbound Medicine. ... Liver_Injury. Drug-Induced Liver Injury. In: Williams D, Ramgopal R, Gdowski M, et al, eds. Washington Manual of Medical ... Liver_Injury. Drug-Induced Liver Injury [Internet]. In: Williams D, Ramgopal R, Gdowski M, Dretler A, Bhat P, editors. ... Liver_Injury. Accessed October 22, 2019.. Drug-Induced Liver Injury. (2016). In Williams, D., Ramgopal, R., Gdowski, M., ...
Red Alert: Drug-Induced Kidney and Liver Injury
... and physicians assistants with an in-depth understanding of common drugs and other agents that are nephrotoxic or hepatotoxic ... Drug-induced kidney and liver injury is a major problem throughout the world. Some of the most commonly prescribed drugs are ... Describe the pathogenesis for drug-induced kidney and liver injury. *State abnormalities in lab results that may indicate ... Identify drugs and supplements that commonly cause kidney and liver toxicity. * ...
Orlistat AND Human[MH] AND (drug induced liver injury OR jaundice/CI O - PubMed - NCBI
... "drug"[All Fields] AND "induced"[All Fields] AND "liver"[All Fields] AND "injury"[All Fields]) OR "drug induced liver injury"[ ... "induced"[All Fields] AND "liver"[All Fields] AND "injury"[All Fields]) OR "chemical and drug induced liver injury"[All Fields] ... Search: Orlistat AND Human[MH] AND (drug induced liver injury OR jaundice/CI OR bile duct diseases/CI OR liver/DE OR liver ... Good outcome of living donor liver transplantation in drug-induced acute liver failure: A single-center experience. ...
PRIME PubMed | How to Diagnose and Exclude Drug-Induced Liver Injury
How to Diagnose and Exclude Drug-Induced Liver Injury. Download Prime PubMed App to iPhone, iPad, or Android ... Clinical features, diagnosis, and natural history of drug-induced liver injury.. *Incidence and Etiology of Drug-Induced Liver ... Chemical and Drug Induced Liver InjuryDatabases, FactualDiagnosis, DifferentialHumansLiverLiver Function TestsRisk Assessment ... The Liver Toxicity Knowledge Base (LKTB) and drug-induced liver injury (DILI) classification for assessment of human liver ...
Drug-Induced Liver Injury Caused by Adalimumab: A Case Report and Review of the Bibliography
Open Access journal that publishes case reports and case series related to the management of disorders affecting the liver, ... Drug-Induced Liver Injury Caused by Adalimumab: A Case Report and Review of the Bibliography. Bernardo Frider,1 Andres Bruno,1 ... We think that adalimumab appears to be responsible for the liver injury, because of temporal relationship, liver biopsy ... We describe a case of a 35-year-old man, with rheumatoid arthritis (RA) and hepatitis C virus genotype 1a with a liver biopsy ...
The Hepatoprotective Effect of Haoqin Qingdan Decoction against Liver Injury Induced by a Chemotherapeutic Drug Cyclophosphamide
Chemical and Drug Induced Liver Injury | CTD
Drug-Induced , Liver Injuries, Drug-Induced , Liver Injury, Drug Induced , Liver Injury, Drug-Induced , Liver Injury, Drug- ... Drug-Induced Liver , Diseases, Drug-Induced Liver , Drug Induced Acute Liver Injury , Drug-Induced Acute Liver Injury , Drug- ... Drug-Induced Liver Disease , Drug-Induced Liver Diseases , Drug-Induced Liver Injuries , Drug Induced Liver Injury , Drug- ... Drug Induced , Hepatitis, Drug-Induced , Hepatitis, Toxic , Injuries, Drug-Induced Liver , Injury, Drug-Induced Liver , Liver ...
Mass. General researchers find novel way to prevent drug-induced liver injury - Massachusetts General Hospital, Boston, MA
Drug-induced liver injury is the most common cause of acute liver failure in the U.S. and is also the most frequent reason for ... General researchers find novel way to prevent drug-induced liver injury. Blocking cell-to-cell communication may prevent liver ... are the most frequent cause of drug-induced liver injury. Compared to normal mice, those lacking liver gap junctions were ... with the ultimate goal of developing liver-safe pharmaceuticals and better treatments for drug-induced liver injury.". Patel is ...
Finding the Pathways to Drug-induced Liver Injury - UConn Today
Drug-induced liver injury is an important public health issue affecting thousands of people around the world annually. It is ... is used worldwide to treat tuberculosis and causes drug-induced liver injury in about 1 percent of all people who take the drug ... investigating whether genes play a role in determining a persons susceptibility to drug-induced liver injury. Ultimately, the ... "For most drug development companies, liver injury is the most important toxicological problem right now," says Boelsterli, the ...
Clinical guidelines issued for drug-induced liver injury
HealthDay)-Herbal and dietary supplements (HDS) account for an increasing proportion of idiosyncratic drug-induced liver injury ... Study finds anti-microbials a common cause of drug-induced liver injury and failure. Nov 30, 2010 ... HealthDay)-Herbal and dietary supplements (HDS) account for an increasing proportion of idiosyncratic drug-induced liver injury ... Antibiotics: Single largest class of drugs causing liver injury More information: Abstract Full Text (subscription or payment ...
Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory...
Circulating microRNAs as potential markers of human drug-induced liver injury. HEPATOLOGY 2011; 5: 1767-1776.. Direct Link: ... Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009; 11: 4402-4407.. * ... Using microRNA as biomarkers of drug-induced liver injury. J Mol Biomark Diagn 2011; 2: 119.. *CrossRef, ... Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory ...
Establishment of Drug-induced Liver Injury Databases and Application of Circulating microRNA(miRNA) - Full Text View -...
Chemical and Drug Induced Liver Injury. Wounds and Injuries. Liver Diseases. Digestive System Diseases. Drug-Related Side ... Liver biopsy is the main method. *clinical features of drug-induced liver injury assessed by serum parameters of liver function ... The purpose of the study is to establish drug-induced liver injury databases in China, make criteria for Chinese drug-induced ... histological features of drug-induced liver injury obtained by liver biopsy [ Time Frame: within six months of the DILI onset ...
Drug-Induced Liver Injury EASL Guideline - EASL-The Home of Hepatology.
EASL Guideline for Drug-Induced Liver Injury. The focus of this EASL Guideline is idiosyncratic Drug-Induced Liver Injury (DILI ... Drug-Induced Liver Injury EASL Guideline. Idiosyncratic (unpredictable) Drug-Induced Liver Injury is one of the most ... Read more about Drug-Induced Liver Injury in the Journal of Hepatology. Also, discover the latest EASL news. ... Therefore, this makes the diagnosis of Drug-Induced Liver Injury an uncertain process. One that requires a high degree of ...
Antimicrobials are Common Cause of Drug-Induced Liver Injury and Failure | Infection Control Today
While ALF evolves slowly, once it does occur a spontaneous recovery is unlikely; however liver transplantation offers an ... leading to acute liver failure (ALF), with women and minorities disproportionately affected. ... a journal of the American Association for the Study of Liver Diseases. ... New research shows that antimicrobial medications are a common cause of drug-induced liver injury (DILI) ...
European Medicines Agency - Non-clinical - Non-clinical evaluation of drug-induced liver injury (DILI)
LncRNA-Regulated Autophagy and its Potential Role in Drug-induced Liver Injury | Annals of Hepatology
Topics covered by AoH include alcoholic liver disease, autoimmune hepatitis, biliary diseases, drug-induced liver injury, ... Drug-induced liver injury (DILI) has gained significant attention worldwide in the last decades on account of its significant ... Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical Features and Predictors of Mortality. ... Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options. ...
Drug-Induced Liver Injury (DILI) Conference XVI | Critical Path Institute
Drug-induced Liver Injury Network (DILIN), the American Association for the Study of Liver Diseases (AASLD), the Hamner-UNC ... Drug-Induced Liver Injury (DILI) Conference XVI. Wednesday, March 23, 2016-. Thursday, March 24, 2016. 7:30AM-5PM. College Park ... Drug Induced Liver Injury (DILI) Conference XV: The Importance of Getting it Right ... DILI Conference XIV: Predicting Serious Drug-Induced Liver Injury in Patients: Who Gets it? Who Doesnt? Why? ...
CiteSeerX - X (2012) Pharmacogenetic study of drug-metabolising enzyme polymorphisms on the risk of anti-tuberculosis drug...
... may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury (ATLI) ranges from a mild to ... In the past decade, many investigations have focused the association between drug-metabolising enzyme (DME) gene polymorphisms ... Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, ... may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury (ATLI) ranges from a mild to ...
Federal Register :: Detecting and Evaluating Drug-Induced Liver Injury; What's Normal, What's Not, and What...
Detecting and Evaluating Drug-Induced Liver Injury; Whats Normal, Whats Not, and What Should We Do About It? This ... The Food and Drug Administration (FDA) is announcing a public conference entitled `` ... "Drug-Induced Liver Injury: Premarketing Clinical Evaluation" (74 FR 38035; July 30, 2009). This guidance explained that drug- ... Detecting and Evaluating Drug-Induced Liver Injury; Whats Normal, Whats Not, and What Should We Do About It?; Public ...
DILIsym® - Drug-induced liver injury (DILI) modeling software
... for use in various stages of the drug development process. ... software for modeling drug-induced liver injury (DILI) ... DILIsym is a "middle-out", multi‑scale representation of drug-induced liver injury. It includes key liver cell populations (e.g ... software designed to be used during drug development to provide an indication of the potential drug-induced liver injury (DILI ... In vitro extrapolation to in vivo predictions (IVIVE) of drug-induced liver injury (DILI) hazard in multiple preclinical ...
Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects
These drugs effectively kills the bacteria but it induced hepatotoxicity known as anti-tuberculosis drug-induced liver injury ( ... rifampicin and pyrazinamide have the potential to induce liver damage.This anti-tuberculosis drug-induced liver injury (ATLI) ... Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects. Print Reference this Disclaimer: This work has been submitted by a ... Most of the TB patients tolerate the drugs but some develop hepatotoxicity known as anti-tuberculosis drug-induced liver injury ...
ATP-Binding-Cassette Transporters in Biliary Efflux and Drug-Induced Liver Injury
... Pedersen, Jenny M. Uppsala University, ... Furthermore, a clear association between BSEP inhibition and clinically reported drug induced liver injuries (DILI) was ... Drug Induced Liver Injury, DILI National Category Pharmaceutical Sciences Identifiers. urn:nbn:se:uu:diva-204168 (URN)10.1093/ ... drug-induced liver injury, DILI, multivariate data analysis, OPLS National Category Pharmaceutical Sciences Research subject. ...
DILIToxicityHepatotoxicityTransplantationHepatitisClinicalHepatologyHepaticIdiosyncratic drug-induced liver injuryDILINCholestasisSevereDiseasesAdverse drug reacDiseaseBiomarkersPatientsHepatocytesMetabolism2020ChronicEnzymesBileIsoniazidHerbalInflammationAcute liver injuryJaundiceOxidative stressAcetaminophen-induced liver injuryCholestatic liverDiagnosisClinicallyInhibition2016HepatocellularMedication-Induced Liver InjuryMedicationsCases of drug-induced liver injuryChemicalCausalityOnsetMetabolites2019Dietary supplementsMortalityTransportersAntibioticsAntituberculosis drugsCause liverHypersensitivityCharacterizationReactionsInteractionsCompounds
- Drug-induced liver injury (DILI) is an injury of the liver that may occur when you take certain medicines. (medlineplus.gov)
- More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. (redorbit.com)
- A robust causality assessment method (CAM) is not only indispensable for the diagnosis of suspected drug-induced liver injury (DILI) and herb-induced liver injury (HILI) but is also critical for the investigation of the clinical features, risk factors, and incidence in pharmacological or epidemiological studies. (springer.com)
- Investigators found that 38 patients with MS positive for the rs2205986 variant had more than an eightfold greater likelihood of drug-induced liver injury (DILI) compared with 113 controls without this genetic feature. (medscape.com)
- DILI remains the leading cause of acute liver failure in the United States. (medscape.com)
- When Kowalec and colleagues added rs2205986 to a predictive model for DILI based on clinical factors alone, the additional information significantly improved prediction of liver injury ( P = .0039). (medscape.com)
- Accumulating evidences reveal that inhibition of BSEP activity is one of the mechanisms for drug-induced liver injury (DILI). (springer.com)
- ABSTRACT: Drug-induced liver injury (DILI) is an uncommon, but potentially fatal, cause of liver disease that is associated with prescription medications, OTC drugs, and herbal and dietary supplements (HDS). (uspharmacist.com)
- Patient, environmental, and drug-related factors may play a role in the pathogenesis of DILI. (uspharmacist.com)
- In the United States, antibiotics and antiepileptic drugs are the most common drug classes associated with DILI, but HDS are on the rise as a cause. (uspharmacist.com)
- The American College of Gastroenterology (ACG) clinical guidelines on idiosyncratic DILI have identified the most common and well-described DILI-associated agents, as well as their pattern of liver injury ( TABLE 1 ). (uspharmacist.com)
- LiverTox (https://livertox.nih.gov) is a clinical and research database developed by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Library of Medicine, and the Drug-Induced Liver Injury Network (DILIN) study group to provide up-to-date, comprehensive clinical information on DILI. (uspharmacist.com)
- 10 Pharmacists should routinely consult LiverTox for the most current information on DILI because there is much variation in standard drug compendia and published reports regarding the potential hepatotoxicity of medicinal products. (uspharmacist.com)
- 11-14 Another drug reference list, DILIrank, contains information on 1,036 FDA-approved medications ranked according to their potential to cause DILI. (uspharmacist.com)
- The National Institutes of Health (NIH) maintains a searchable database of over 1000 drugs, herbal medications, and dietary supplements that have been associated with drug-induced liver injury (DILI) at http://livertox.nih.gov/ . (unboundmedicine.com)
- Acute DILI progresses to chronic injury in 5%-10% of cases. (unboundmedicine.com)
- The diagnosis of drug-induced liver injury (DILI) is largely a diagnosis of exclusion because, with the possible exception of protein:drug adducts in paracetamol overdose, there are no laboratory, biopsy or imaging tests that alone are capable of establishing an unequivocal diagnosis of DILI. (unboundmedicine.com)
- However, it is increasingly appreciated that drugs that cause DILI typically have characteristic clinical presentations or 'signatures' that can be very useful in the diagnosis of DILI. (unboundmedicine.com)
- Indeed, knowing a drug's DILI signature (or sometimes signatures) and the incidence rate of DILI during treatment with that drug are perhaps the most useful pieces of historical information in arriving at the diagnosis of DILI. (unboundmedicine.com)
- A major advance has been the establishment of the LiverTox website (http://livertox.nih.gov/) which provides open access to standardized entries for over 600 different drugs, including the characteristic clinical presentations of DILI when known. (unboundmedicine.com)
- The person entering data must therefore subjectively weigh the RUCAM score with the characteristic DILI signature(s) of the drug to arrive at a diagnosis. (unboundmedicine.com)
- In the future, it should be possible to construct improved diagnostic instruments that objectively incorporate DILI signatures, data-based estimates of the incidence rates of DILI from each implicated drug, and perhaps genetic variants associated with the risk of DILI. (unboundmedicine.com)
- HealthDay)-Herbal and dietary supplements (HDS) account for an increasing proportion of idiosyncratic drug-induced liver injury (DILI), according to practice guidelines published online June 17 in the American Journal of Gastroenterology . (medicalxpress.com)
- The focus of this EASL Guideline is idiosyncratic Drug-Induced Liver Injury (DILI). (easl.eu)
- Intrinsic DILI is typically dose-related and occurs in a large proportion of individuals exposed to the drug (predictable) and onset is within a short time span (hours to days). (easl.eu)
- New research shows that antimicrobial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure (ALF), with women and minorities disproportionately affected. (infectioncontroltoday.com)
- Patients with liver failure resulting from DILI may experience deep jaundice, fluid retention, advanced coagulopathy and coma. (infectioncontroltoday.com)
- Our findings confirm prior medical evidence that found a high female predominance in DILI ALF, suggesting that women may be more susceptible to liver injury or use more prescription drugs than men," says Dr. Adrian Reuben, professor of medicine at the Medical University of South Carolina and lead study author. (infectioncontroltoday.com)
- Anti-microbial agents were found to be the most common cause of DILI ALF cases and included anti-tuberculosis drugs (25), sulphur-containing drugs (12), nitrofurantoin (12), other antibiotics (7), antifungal agents (6), and anti-retroviral drugs (4). (infectioncontroltoday.com)
- This study aimed to review recently published studies and further describe the long noncoding RNA (lncRNA)-regulated autophagy during drug-induced liver injury (DILI). (elsevier.es)
- Many studies explicitly indicated that DILI and its progression to acute liver failure were causatively linked to endoplasmic reticulum stress and subsequently induced autophagy, which protect hepatocytes during DILI. (elsevier.es)
- DILIsym is Quantitative Systems Toxicology (QST) software designed to be used during drug development to provide an indication of the potential drug-induced liver injury (DILI) hazard posed by individual molecules and/or to provide deeper insight into the mechanisms responsible for observed DILI responses at various stages of the development process. (simulations-plus.com)
- Furthermore, a clear association between BSEP inhibition and clinically reported drug induced liver injuries (DILI) was identified. (diva-portal.org)
- Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). (sigmaaldrich.com)
- Drug-Induced Liver Injury (DILI) is one of the most common adverse drug event leading to drug candidate termination and post marketing drug withdrawal. (complianceonline.com)
- Are you and others in your organization aware of the many mechanisms known to cause Drug-Induced Liver Injury (DILI)? (complianceonline.com)
- The webinar will dig deep into the most common strategies used by drug hunters and will describe the relevant assays and models used to characterize and mitigate DILI risks. (complianceonline.com)
- He has specific expertise in the mechanisms and mitigation strategies to avoid drug-induced liver injury (DILI). (complianceonline.com)
- Our aim was to explore drug-induced liver injury (DILI) in Switzerland using the real-world data of the global pharmacovigilance database VigiBase™, with a special focus on the new drug class of checkpoint inhibitors. (smw.ch)
- Hepatic adverse drug reactions are an important issue in drug safety: DILI (drug-induced liver injury) is the leading cause of acute liver failure in the United States and Europe [ 1 , 2 ]. (smw.ch)
- The consequences may be severe: it was estimated that within 6 months of onset of DILI, almost 10% of patients undergo liver transplantation or die, and nearly 20% may suffer persistent liver injuries [ 3 ]. (smw.ch)
- Furthermore, DILI is considered one of the most common causes of compound attrition in drug development and for withdrawal of drugs from the market [ 4 ]. (smw.ch)
- Because of the limited predictive value of pre-clinical assays and the limited power of pre-marketing clinical trials to detect rare safety and toxicity issues, large drug registries and spontaneous reporting systems of adverse drug reactions have a critical role in the early identification of safety signals, especially for rare idiosyncratic events such as DILI. (smw.ch)
- Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. (aspetjournals.org)
- Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. (uzh.ch)
- From the numerous in vitro test systems that are available, monocyte-derived hepatocytes generated from patients with DILI show promise in identifying the DILI-causing agent from among a panel of coprescribed drugs. (uzh.ch)
- The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public-private partnerships. (uzh.ch)
- To assess the proportion of significant drug-induced liver injury (DILI) due to tuberculosis treatment (TBT) and/or antiretroviral therapy (ART) among patients presenting with liver dysfunction at GFJH and to describe management and outcomes. (scielo.org.za)
- TBT- or ART-associated DILI was defined as significant liver dysfunction attributed to TBT and/or ART and which resulted in the halting of treatment or the adjustment thereof. (scielo.org.za)
- A total of 318/354 cases of significant liver dysfunction were reviewed: 71 were classified as TBT- or ART-associated DILI, while liver dysfunction was attributed to other causes in the remainder. (scielo.org.za)
- Drug-induced liver injury (DILI) refers to acute or chronic liver injury that may occur as a consequence of using drugs and herbal or dietary supplements. (biomedcentral.com)
- While these genetic variations have been shown to increase the risk for the development of DILI, they do not predict severity of injury. (biomedcentral.com)
- Also, withdrawals of these lucrative drugs diminish the return on substantial investments by drug makers and threaten further R&D. Hence, elucidating the mechanisms by which DILI occurs early in drug discovery is an important focus of pharmaceutical research. (discoverx.com)
- In the present study, we investigated feasibility of the BioMAP (part of DiscoveRx) technology platform to understand the mechanisms of DILI of marketed drugs using primary human cells, stimulated under a variety of conditions mimicking disease biology. (discoverx.com)
- My research group is particularly interested in using different models to gain a better understanding of the role of the mitochondria in drug-induced liver injury (DILI). (liverpool.ac.uk)
- Whilst HepG2 cells are the most common cell line used to investigate mitochondrial dysfunction in DILI, they are not very 'liver-like' in comparison with human liver cells. (liverpool.ac.uk)
- ABCB11 ) has been proposed to play a role in drug-induced liver injury (DILI). (aspetjournals.org)
- A clear distinction was not evident between hBSEP IC 50 or unbound plasma concentration ( C max, u ) of the drugs in humans and whether the drugs caused DILI. (aspetjournals.org)
- Failure of drugs during late phases of the drug discovery process costs the pharmaceutical industry billions of dollars each year, and drug-induced liver injury (DILI) is the primary reason for post-market drug withdrawal. (technologynetworks.com)
- InSphero 3D InSight™ Human Liver Microtissues provide a more sensitive preclinical in vitro model for DILI detection and prediction, with the specificity to accurately distinguish between known hepatotoxicants and structurally-related non-toxic analogs. (technologynetworks.com)
- Idiosyncratic drug-induced liver injury (DILI) is a rare disease that develops independently of drug dose, route, or duration of administration. (semanticscholar.org)
- Objective: To review all cases of drug-induced liver injury (DILI) requiring hospitalization at a single tertiary care center. (elsevier.com)
- In the NA-DILI group, mean age was 59 ± 17.9 years and liver injury was classified as hepatocellular (7), cholestatic (5), or mixed (1). (elsevier.com)
- Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. (tropicalgastro.com)
- Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. (tropicalgastro.com)
- Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. (tropicalgastro.com)
- Hepatotoxicity or DILI due to antituberculosis drug-induced liver injury (DILI) encompasses a wide spectrum of liver injury ranging from asymptomatic minimal elevation of liver enzymes to acute liver failure, often leading to death or liver transplantation. (tropicalgastro.com)
- [8 , 9 , 10] In contrast, non-TB antibiotics and paracetamol are the commonest causes of DILI and drug-induced ALF in western countries. (tropicalgastro.com)
- 11 , 12 , 13] In a single center registry of 303 patients from Bangalore, antituberculosis drugs contributed to 58% cases of DILI. (tropicalgastro.com)
- What are the signs and symptoms of drug-induced liver injury (DILI)? (antibioticliverdamage.com)
- Antibiotics are the single largest class of agents that cause idiosyncraticdrug-induced liver injury (DILI)," reports a study published in Gastroenterology , the official medical journal of the American Gastroenterological Association (AGA) Institute. (antibioticliverdamage.com)
- Our bioinformatic analysis indicates that there may be a connection between the different HLA alleles associated with DILI caused by therapeutically and structurally different drugs, possibly through peptide binding of one of the HLA alleles that defines the causal haplotype. (biomedcentral.com)
- In addition, extracutaneous organ involvement, such as drug-induced liver injury (DILI) can also occur, either in combination with skin involvement or in isolation. (biomedcentral.com)
- Background & Aims The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. (elsevier.com)
- Conclusions Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. (elsevier.com)
- Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. (elsevier.com)
- Idiosyncratic drug-induced liver injury (DILI) is, like other adverse effects of drugs, underreported and underestimated in most epidemiological studies based on registries of DILI cases and reporting systems (e.g. (qxmd.com)
- Drug-induced liver injury associated with intravenously given drugs does not show any major differences from DILI due to orally administered agents. (qxmd.com)
- Drug-induced liver injury (DILI) is an uncommon adverse drug reaction of increasing importance to the medical community, pharmaceutical industry, regulatory agencies and the general public. (qxmd.com)
- The Drug-Induced Liver Injury Network (DILIN) was established to advance understanding and research into DILI by initiating a prospective registry of patients with bona fide DILI for future studies of host clinical, genetic, environmental and immunological risk factors. (qxmd.com)
- Eligible patients are required to meet minimal laboratory or histological criteria within 6 months of DILI onset and have other competing causes of liver injury excluded. (qxmd.com)
- This causes certain patients to suffer from drug-induced liver injury (DILI), where there are unexpected side effects from consuming a drug, causing liver damage. (nus.edu.sg)
- The research team found that rats suffering from DILI (DILI rats) experienced a process termed "enhanced enterohepatic recycling", where the excreted metabolite of the drug in bile is reconverted back to the parent drug by gut bacteria and reabsorbed into the body from within the gut. (nus.edu.sg)
- The DILI rats were found to have a greater amount of a specific bacteria that can enable this drug reconversion process. (nus.edu.sg)
- Our experienced investigator team is dedicated to establishing an authoritative, complete and current internet website devoted to drug-induced liver injury (DILI). (grantome.com)
- Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. (lsh.is)
- Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. (lsh.is)
- This entry was posted in Pediatric Gastroenterology Liver Disease and tagged acetaminophen , acute liver failure , Alpers syndrome , DILI , drug-induced liver disease , valproic acid by gutsandgrowth . (gutsandgrowth.com)
- Drug-induced liver injury (DILI) is a persistent matter in the pharmaceutical field, with extensive research being dedicated to understanding the causes, risk factors, and potential biomarkers associated with it. (umaryland.edu)
- While DILI manifests in a variety of ways and diseases, the most severe form is drug-induced cholestasis. (umaryland.edu)
- Drug-induced liver injury (DILI) affects thousands of patients every year, and is the most common reason for both medication withdrawal and U.S. Food and Drug Administration (FDA) regulatory actions concerning drugs. (dcri.org)
- Up to 9 percent of all adverse drug reactions reported to health authorities come from DILI, and several hundred medications and herbal and dietary supplements have been implicated. (dcri.org)
- Establishing a diagnosis of DILI can be tricky due to the presence of other potential causes, and the injury can range from mild and transient to severe and protracted, according to Barnhart. (dcri.org)
- That suggests a hallmark symptom of drug-induced liver injury (DILI), says Robert J. Fontana, M.D. , a hepatologist and Medical Director of the Liver Transplant Program at University of Michigan Health System. (uofmhealth.org)
- Drug-induced liver injury (DILI) is the leading cause of acute liver failure leading to death or requiring transplantation in the European Union (EU) and USA. (emjreviews.com)
- 1-3 Due to the potentially severe consequences of DILI, it is also among the most frequent causes for regulatory actions on drugs, such as marketing restrictions, clinical hold of studies, and market withdrawal. (emjreviews.com)
- This dose-dependent or intrinsic DILI is a characteristic of the drug causing liver injury in every patient exposed to an overdose exceeding a given threshold (e.g., 150 mg/kg bodyweight for acetaminophen). (emjreviews.com)
- In patients presenting with dose-dependent DILI, the history (intake of overdose) and toxicological investigations are used to identify the cause of liver injury. (emjreviews.com)
- OBJECTIVES: To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea. (yu.ac.kr)
- Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). (cdc.gov)
- We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. (cdc.gov)
- To better understand the clinical significance of drug induced liver injury (DILI) during chemotherapy, we examined the epidemiology, incidence, and treatment effects of DILI in patients undergoing chemotherapy for genitourinary malignancies over a twoyear period. (imedpub.com)
- Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications. (cdc.gov)
- There is a critical need to develop a means of predicting, detecting and diagnosing drug (or herbal product)-induced liver injury (DILI) in the United States. (unc.edu)
- In 2004, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the Drug-Induced Liver Injury Network (DILIN) to conduct clinical and basic science studies of DILI. (unc.edu)
- 약인성 간손상(Drug-induced liver injury, DILI)은 혈청학적 검사 소견 상 간 손상이 관찰되었고, 약물의 투약이 간손상의 확인 시점 이전에 선행된 사실이 있으며, 투약된 약물 이외에 다른 간손상 유발인자에 대한 노출을 배제할 수 있으나, 조직학적 검사가 동반되지 않아 간염 및 간경변 등으로 확진할 수 없는 경우에 내릴 수 있는 진단이다 1 . (jikm.or.kr)
- The goal of the ILIAD protocol is to create a database and bank of biological specimens (DNA, plasma, lymphocytes) from individuals with severe drug-induced liver injury (DILI) due to drugs, or herbal and dietary supplements (HDS) and complementary and alternative medications (CAM) after January 1, 1994. (umich.edu)
- For a wide variety of drugs a correlation has also been observed between propensity to cause DILI in humans, potency of in vitro BSEP inhibition and their therapeutic plasma drug concentrations. (solvobiotech.com)
- These findings suggest that BSEP inhibition could be an important mechanism which helps explain how some drugs initiate DILI. (solvobiotech.com)
- Drug-induced liver injury (DILI) is a major safety concern characterized by a complex and diverse pathogenesis. (beds.ac.uk)
- In order to identify DILI early in drug development, a better understanding of the injury and models with better predictivity are urgently needed. (beds.ac.uk)
- In the models which used predicted protein targets as compound descriptors, we identified the most information-rich proteins which agreed with the mechanisms of action and toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most important drug classes causing DILI, stress response via TP53 and biotransformation. (beds.ac.uk)
- Drug-induced liver injury (DILI) is a major safety concern and one of the leading causes of drug failure in clinical drug development and market withdrawal, which can be found across nearly all classes of medication [ 1 ]. (beds.ac.uk)
- DILI may occur either as hepatitis or cholestatic injury or a mixed form of both and can be further distinguished between intrinsic and idiosyncratic DILI [ 1 ]. (beds.ac.uk)
- If a drug is hepatotoxic in a dose-dependent manner both in preclinical models and humans (e.g. acetaminophen) it is considered to cause intrinsic DILI. (beds.ac.uk)
- In contrast to intrinsic DILI, idiosyncratic DILI is the result of a patient's rare combination of genetic and non-genetic risk factors, which is responsible for their susceptibility towards the drug [ 2 ]. (beds.ac.uk)
- Due to the low incidence of DILI, revealing causal links between the use of a drug and an observed liver injury is a difficult task [ 4 ], which decreases the confidence in provided DILI labels and further complicates the building of QSAR models with high predictivity. (beds.ac.uk)
- Patients with multiple sclerosis (MS) who carry a specific genetic variant identified through genome-wide testing are at significantly elevated risk for liver toxicity when treated with interferon-β, new research reveals. (medscape.com)
- However, adverse effects like liver toxicity can occur in up to 1 in 50 people treated with this drug," co-lead author Kaarina Kowalec, PhD, from the Division of Neurology, Faculty of Medicine, University of British Columbia in Vancouver, Canada, at the time of the study, told Medscape Medical News . (medscape.com)
- This is why we wanted to look for genomic biomarkers to help predict who might be at higher risk for experiencing liver toxicity such that a more precise or personalized treatment plan could be developed. (medscape.com)
- Some of the most commonly prescribed drugs are involved in the pathogenesis of kidney and liver toxicity, including antibiotics, acetaminophen (Tylenol), NSAIDs (e.g., ibuprofen), and ACE inhibitors. (nurse.com)
- To further compound this issue, many agents that cause kidney or liver toxicity are available over the counter. (nurse.com)
- Therefore, it is imperative that nurses, physicians, physician's assistants, nurse practitioners, and pharmacists are aware of which agents commonly cause kidney or liver injury, symptoms that may indicate toxicity, abnormalities in lab values that indicate kidney or liver injury, and potential preventive measures. (nurse.com)
- The goal of this continuing education program is to provide physicians, pharmacists, nurses, nurse practitioners, and physician's assistants with an in-depth understanding of common drugs and other agents that are nephrotoxic or hepatotoxic, while providing them with the tools needed to perform their roles as members of the healthcare team working collaboratively to prevent and manage cases of kidney and liver toxicity. (nurse.com)
- This work also has the potential to change the way drugs are developed and formulated, which could improve drug safety by providing medications with reduced risk of liver toxicity. (massgeneral.org)
- Liver toxicity limits the development of many therapeutic compounds and presents major challenges to both clinical medicine and to the pharmaceutical industry. (massgeneral.org)
- In vitro studies for drug toxicity, such as the one being performed at UConn, are a new and promising step toward greater understanding. (uconn.edu)
- This document reviews current approaches to the detection of drug-induced hepatotoxicity alerts in non-clinical, regulatory toxicity studies. (europa.eu)
- DILIsym simulations integrate compound exposure with compound mediated mechanisms of intrinsic drug toxicity, and with inter-individual variability. (simulations-plus.com)
- DILIsym prospectively supports key management decisions by providing information about potential drug-induced liver injury risk in upcoming experimental or clinical study designs, as well as mechanistic rationale for the underlying biochemical events that could cause liver toxicity. (simulations-plus.com)
- DILIsym has been developed within a conceptual framework (Figure 1), wherein liver compound exposure (parent and/or metabolite) can engage various mechanisms of intrinsic toxicity. (simulations-plus.com)
- Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. (diva-portal.org)
- Importantly, I was able to show that mitochondrial dysfunction was not a mechanism of bile acid-induced toxicity, contrary to the accepted understanding based upon data from simpler models (PMID: 31288073). (liverpool.ac.uk)
- We know that not everyone who receives a drug will experience toxicity and so determining what makes these individuals more susceptible to toxicity is paramount for improving drug safety. (liverpool.ac.uk)
- Melamine-induced renal toxicity is mediated by the gut microbiota. (semanticscholar.org)
- Drug toxicity, and drug-induced liver injury in particular, is a major reason for failures in clinical trials and for the withdrawal of previously approved drugs from the market. (thefreedictionary.com)
- Developing liver toxicity with valproic acid (VPA) is a contraindication to OLTx (even in the absence of documented mitochondrial dz). (gutsandgrowth.com)
- 4 MH cells were generated from patients and exhibited donor-specific characteristics, most importantly, an enhanced toxicity response in vitro towards drugs that have been shown to cause iDILI in the respective patient. (emjreviews.com)
- The authors suggest that slower metabolic processing of efavirenz resulting in lower peak levels of the drug and less central nervous system toxicity, observed in some African populations, might explain the result. (aidsmap.com)
- Hepatotoxicity (from hepatic toxicity ) implies chemical-driven liver damage. (wikipedia.org)
- The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. (wikipedia.org)
- Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for drug screening assays, such as stem cell -derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. (wikipedia.org)
- Drugs or toxins that have a pharmacological (type A) hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity, such as directly damaging liver tissue or blocking a metabolic process. (wikipedia.org)
- As in the case of acetaminophen overdose, this type of injury occurs shortly after some threshold for toxicity is reached. (wikipedia.org)
- Nitric oxide also plays a role in inducing toxicity. (wikipedia.org)
- A research team led by Prof HO Han Kiat from the Department of Pharmacy, NUS has discovered the mechanisms involved when minor chemical modifications such as a single substitution of a small halogen or alkyl group (functional groups in chemical structures) of pharmaceutical drugs alters the toxicity profile of the drugs. (phys.org)
- By understanding the specific mechanisms contributing to the toxicity, pharmaceutical scientists can modify the chemical structure so as to develop drugs which are more effective and safe. (phys.org)
- As part of the research, the team used a pair of anti-inflammatory drugs, diclofenac and lumiracoxib, that differ minimally in terms of structure, but exhibit profound differences in terms of toxicity. (phys.org)
- Diclofenac is a relatively safe painkiller still in wide usage today, while lumiracoxib has been withdrawn from the market due to severe liver toxicity. (phys.org)
- Many other compounds with small chemical changes were also synthesised and evaluated for their potential to cause toxicity and how they may be metabolised differently in liver cells. (phys.org)
- Björnsson ES (2016) Hepatotoxicity by drugs: the most common implicated agents. (springer.com)
- also known as drug-induced hepatotoxicity ) is caused by medications (prescription or OTC), herbal and dietary supplements (HDS), or other xenobiotics that result in abnormalities in liver tests or in hepatic dysfunction that cannot be explained by other causes. (uspharmacist.com)
- These drugs effectively kills the bacteria but it induced hepatotoxicity known as anti-tuberculosis drug-induced liver injury (ATLI) [5.tostmann 2008]. (ukessays.com)
- Although hepatotoxicity accounts for 10% of adverse drug reactions, it remains poorly understood and underreported. (elsevier.es)
- Resolution occurred in seven, two died of complications related to hepatotoxicity, one underwent liver transplantation, and the outcome was undetermined in three who were lost to follow-up. (elsevier.com)
- Although a vast majority of patients tolerate the drugs, some develop adverse effects of which hepatotoxicity is the most significant. (tropicalgastro.com)
- [8 , 9] Furthermore, the ripple effects of hepatotoxicity include disruption of treatment with potential for prolongation of treatment, genesis of drug resistance and suboptimal cure. (tropicalgastro.com)
- Although statin-induced hepatotoxicity has been well documented, the risk is probably quite low. (qxmd.com)
- Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in VigiBase: unified list based on international collaborative work. (qxmd.com)
- Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug-Induced Liver Injury Network (DILIN). (qxmd.com)
- Chan ECY*, "The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat" HEPATOLOGY DOI: 10.1002/hep.29327 Published: 2017. (nus.edu.sg)
- Drug-related hepatotoxicity and acute liver failure. (gutsandgrowth.com)
- Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. (nih.gov)
- Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins ) and herbal remedies can also induce hepatotoxicity. (wikipedia.org)
- Idiosyncratic (type B) injury occurs without warning, when agents cause non-predictable hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period. (wikipedia.org)
- Hepatotoxicity may manifest as triglyceride accumulation which leads to either small droplet (microvesicular) or large droplet (macrovesicular) fatty liver. (medicotips.com)
- The most commonly implicated drugs were amoxicillin-clavulante (penicillin used to fight bacteria), azathioprine (an immunosuppressive drug used in organ transplantation and autoimmune diseases) and infliximab (also used to treat autoimmune disease). (redorbit.com)
- Explain to patients that acetaminophen is the leading cause of drug-induced severe liver damage and often requires transplantation. (medpagetoday.com)
- But caution them that young people taking antiepileptic drugs who develop drug-induced liver injury have a higher likelihood of death with liver transplantation. (medpagetoday.com)
- RIDGEWOOD, N.J., July 5 -- Acetaminophen leads the list of drugs implicated in liver damage requiring transplantation, although antiepileptics are more lethal, according to a new study. (medpagetoday.com)
- 0.0001), the investigators reported in the July issue of Liver Transplantation . (medpagetoday.com)
- As potentially hazardous to the liver as acetaminophen may be, the risk of death following liver transplantation was highest among patients whose liver injury was caused by antiepileptics, Dr. Mindikoglu found. (medpagetoday.com)
- In an accompanying editorial, Paul H. Hayashi, MD, and Paul Watkins, MD, of the University of North Carolina, wrote that this is the first study to propose a mathematical model to predict survival after transplantation for acute liver failure. (medpagetoday.com)
- Drug-induced liver injury is a relatively rare, but potentially life-threatening type of liver disease that is a growing cause of death and of the need for liver transplantation in the United States. (nih.gov)
- As part of the prospective study conducted by the Network, researchers analyzed how frequently participants with drug-induced liver injury experienced what were considered "fatal outcomes"-either death or liver transplantation, without which the individual would have died-over the following 2 years. (nih.gov)
- Experts reviewed the case details to assess whether the injury was a primary cause of death or life-saving transplantation, or if it was simply one contributing factor. (nih.gov)
- During this time, 26 (7 percent) of the study participants who had liver biopsies showed signs of bile duct loss, from which seven individuals died and two others eventually required liver transplantation. (nih.gov)
- The degree of the bile duct loss was found to be the best predictor of poor outcomes, such as death or need for a liver transplantation. (nih.gov)
- Good outcome of living donor liver transplantation in drug - induced acute liver failure: A single-center experience. (nih.gov)
- Since no pharmaceutical strategies currently exist for preventing drug-induced liver injury, treatment options are limited to discontinuing the offending drug, supportive care and transplantation for end-stage liver failure. (massgeneral.org)
- Multiple barriers limit the number of HCV-HIV coinfected patients who receive antiviral therapy for HCV, and the role of orthotopic liver transplantation (OLT) in HIV monoinfected and HCV-HIV coinfected patients remains controversial. (nih.gov)
- however liver transplantation offers an excellent survival rate. (infectioncontroltoday.com)
- There were 56 eligible subjects who underwent liver transplantation of whom all but four survived, giving an overall survival for the entire cohort 66.2 percent. (infectioncontroltoday.com)
- Liver transplantation offers excellent survival for ALF patients, however further investigation should include more detail on drug use duration, and the impact of alcohol use and diabetes, to provide additional understanding of idiosyncratic drug-induced liver injury and failure," Reuben adds. (infectioncontroltoday.com)
- Journal of Liver: Disease & Transplantation. (scitechnol.com)
- Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. (elsevier.com)
- Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. (elsevier.com)
- Liver transplant links and resources are at the Center for Transplantation . (ucsd.edu)
- The mission of the American Association for the Study of Liver Diseases is to advance the science and practice of hepatology, liver transplantation and hepatobiliary surgery. (ucsd.edu)
- Those that develop acute liver failure can still recover spontaneously, but may require transplantation if poor prognostic signs such as encephalopathy or coagulopathy is present (see King's College Criteria ). (wikipedia.org)
- The most severe functional consequence is Progressive Familial Intrahepatic Cholestasis type 2, which is characterised by early onset cholestasis soon after birth and subsequent progressive degenerative liver injury that is fatal unless treated by liver transplantation. (solvobiotech.com)
- Some drugs can cause hepatitis with small doses, even if the liver breakdown system is normal. (medlineplus.gov)
- Many different drugs can cause drug-induced hepatitis. (medlineplus.gov)
- There is urgent need to update and revise thinking to consider investigational treatment of patients with pre-existing liver diseases such as chronic viral infection with hepatitis C or B, alcoholic and non-alcoholic steatohepatitis, and other liver disorders. (c-path.org)
- For checkpoint inhibitors, hepatitis was the most frequently reported hepatic adverse drug reaction. (smw.ch)
- We are watching to see whether the FDA and/or European drug regulators require a Pradaxa liver injury label change adding a new warning about an increased risk of acute liver failure and drug-induced hepatitis - like what was done in Japan last year and is being done now in Canada. (lamblawoffice.com)
- The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. (tropicalgastro.com)
- People who already display a degree of liver damage, such as some hepatitis and diabetes patients, are especially at risk of developing complications after ingesting antibiotics and a broad range of other prescription and over-the-counter drugs as well. (antibioticliverdamage.com)
- Patients in the general community setting with pre-existing HIV, hepatitis B virus or hepatitis C virus infections and/or abnormal baseline liver biochemistries are eligible for enrollment. (qxmd.com)
- Drugs that cause symptomatic hepatitis: abdominal pain, jaundice, loss of appetite. (gutsandgrowth.com)
- In 2013, more than 40 cases of acute hepatitis, including several instances of acute, fatal liver failure, were linked to the same product. (dcri.org)
- The primary focus of the Asian Health Foundation is hepatitis B. Hepatitis B affects 1 in 10 Asian Americans and is a leading cause of liver cancer among this demographic. (ucsd.edu)
- Education classes and support groups for people who have hepatitis C and liver cancer are available. (ucsd.edu)
- Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells. (cdc.gov)
- Mount Sinai provides personalized care, whatever type of acute or chronic liver disease you may have, including hepatitis B and hepatitis C, liver cancer, or cirrhosis . (mountsinai.org)
- The staff of the Liver Program maintains a genomic DNA bank of samples collected in an ongoing antiviral protocol for hepatitis C. This bank is part of a collaboration with the Translational and Clincal Sciences Institute. (unc.edu)
- Drug-induced hepatitis with granulomata . (wikipedia.org)
- Hepatitis B vaccine is associated with an increased risk of liver problems in U.S. children less than 6 years old, 1993 and 1994. (greenmedinfo.com)
- Nine patients presented with cholestatic hepatitis and 12 patients presented with hepatocellular injury, of which six had an autoimmune phenotype. (elsevier.com)
- There can be three types of drug-induced hepatitis. (medicotips.com)
- Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. (medscape.com)
- Hepatitis E (HEV) was initially identified in the late 1970s as an epidemic non-A non-B hepatitis that caused an infectious water-borne illness similar to hepatitis A. [ 1 ] Now, HEV is a leading cause of icteric hepatitis and acute liver failure in the developing world. (medscape.com)
- ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. (medlineplus.gov)
- Ortega-Alonso A, Stephens C, Lucena MI, Andrade RJ (2016) Case characterization, clinical features and risk factors in drug-induced liver injury. (springer.com)
- The investigators reviewed medical records for each patient to collect demographic and clinical information, including a comprehensive assessment of adverse drug reactions. (medscape.com)
- Lam P, Soroka CJ, Boyer JL (2010) The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. (springer.com)
- Diagnosis and prognosis is complicated by the varying patterns of clinical injury observed to the liver and to the ducts carrying bile away from the liver to the intestine, sometimes resulting in liver failure. (nih.gov)
- The investigators also tested three mathematical formulas used to predict mortality risk from liver disease based on clinical measures, such as liver enzymes, bilirubin, and creatinine. (nih.gov)
- Most of these individuals first presented with a type of clinical pattern marked by severe injury to the bile ducts and liver inflammation. (nih.gov)
- We think that adalimumab appears to be responsible for the liver injury, because of temporal relationship, liver biopsy findings, other clinical conditions being discarded, and the improvement of clinical symptoms and biochemical abnormalities when adalimumab was suspended. (hindawi.com)
- A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. (mdibl.org)
- This happens because of the myriad of drugs used in clinical practice. (easl.eu)
- This Clinical Practice Guideline summarizes the available evidence on risk factors, diagnosis, management, risk minimization strategies for Drug-Induced Liver Injury . (easl.eu)
- Our journal seeks to publish articles on basic clinical care and translational research focused on preventing rather than treating the complications of end-stage liver disease. (elsevier.es)
- How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials? (c-path.org)
- Clinical trials in humans exposed to new drugs being developed provide data for the regulatory decisions on approval/non-approval but also provide the best information to guide optimal use postmarketing by prescribers in treating patients. (c-path.org)
- After three years at Monsanto/Searle, Bryan joined Eli Lilly and Company in 1993, where he led multiple cross functional drug discovery efforts, many of which culminated in clinical candidates for oncology, endocrine and pain indications. (complianceonline.com)
- Further clinical studies are warranted to directly compare hepatic adverse drug reactions to different checkpoint inhibitors. (smw.ch)
- Drug induced liver injury, in particular the idiosyncratic type (IDILI), is extremely difficult to identify before a compound reaches the later stages of drug development, often not being detected until the clinical trials or when the drug is approved and in the market. (discoverx.com)
- Two of 6 dogs that received the highest dose of TAK-875 developed liver injury with clinical pathology changes, and by microscopic analysis had portal granulomatous inflammation with neutrophils around a crystalline deposition. (ovid.com)
- The inflammatory mediator, high mobility group box 1 (HMGB1), is a key regulator of a range of liver injury conditions and is elevated in clinical and preclinical APAP-ALI. (ovid.com)
- Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. (semanticscholar.org)
- Causes, clinical features, and outcomes from a prospective study of drug-Induced liver injury in the United States 'abstract]. (thefreedictionary.com)
- A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment. (childrensmercy.org)
- Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. (qxmd.com)
- The UNC-Chapel Hill clinical center has been a leader in the Drug-Induced Liver Injury network (DILIN) from its inception, in terms of subject recruitment, data quality, biospecimen collection, and ancillary study proposals. (grantome.com)
- We provide LiverTox with a case registry to help with scientific analysis and the clinical patterns of liver injury," said Barnhart. (dcri.org)
- Since iDILI is a rare event most often encountered when a drug is used by a number of patients (e.g., in a late-stage clinical trial or post-marketing), much effort is being made to identify biomarkers that help to predict severe iDILI and/or identify susceptible patients. (emjreviews.com)
- We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. (cdc.gov)
- The TDOC is a seven center consortium that will consolidate clinical data related to pre and post liver transplant patients. (unc.edu)
- Liver injury leads to impairment of bile flow and the clinical picture is predominated by itching and jaundice. (medicotips.com)
- Dr. Kenna provides expert advice to clients within the healthcare sector on generation and interpretation of preclinical and clinical safety data and is committed to the development and implementation of improved and mechanistically based drug safety screening and risk assessment strategies. (solvobiotech.com)
- Where many other hepatology textbooks provide detailed accounts of basic science and clinical management, Sherlock's Diseases of the Liver and Biliary System, 13th Edition takes a different approach. (wiley.com)
- In these studies, nilutamide monotherapy at a dosage of 300 mg/day, induced observable signs of clinical feminization in young transgender women (age range 19-33 years) within 8 weeks, including breast development, decreased body hair (though not facial hair), decreased morning erections and sex drive, and positive psychological and emotional changes. (wikipedia.org)
- Drug-induced liver injury is not a single, uncommon disease of the general population, but rather a series of rare diseases that occur only in persons who take specific medications," said Einar S. Björnsson, lead study author from the department of internal medicine, section of gastroenterology and hepatology, National University Hospital, Reykjavik, Iceland, and faculty of medicine at the University of Iceland. (redorbit.com)
- Full findings of this 10-year prospective study are published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases. (infectioncontroltoday.com)
- It is the official journal of the Mexican Association of Hepatology ( AMH ), the Latin American Association for the Study of the Liver ( ALEH ), the Canadian Association for the Study of the Liver ( CASL ) and the Czech Society of Hepatology ( CSH ). (elsevier.es)
- It is the official journal of the Mexican Association of Hepatology (AMH), the Latin-American Association for the Study of the Liver (ALEH) and the Canadian Association for the Study of the Liver (CASL) and publishes original papers, concise reviews, letters to the Editor, invited editorials, opinions and viewpoints in the field of Hepatology. (elsevier.es)
- Orlistat - induced fulminant hepatic failure. (nih.gov)
- Estrogens and oral contraceptives are both associated with several liver related complications including intrahepatic cholestasis, sinusoidal dilatation, peliosis hepatis, hepatic adenomas, hepatocellular carcinoma, hepatic venous thrombosis and an increased risk of gallstones. (wellnessresources.com)
- Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4. (sigmaaldrich.com)
- This is the first study investigating drug-related hepatic disorders in Switzerland in a global pharmacovigilance database. (smw.ch)
- For data extraction, the standardised MedDRA query (SMQ) "narrow drug-related hepatic disorders - severe events only" was applied. (smw.ch)
- For comparing the hepatic adverse drug reactions of pembrolizumab, nivolumab and ipilimumab, the reporting odds ratios (RORs) were calculated in a disproportionality analysis. (smw.ch)
- Paracetamol, amoxicillin/clavulanic acid, esomeprazole and atorvastatin ranked among the most frequently suspected drugs for severe drug-related hepatic disorders. (smw.ch)
- Because of the frequency and severity of hepatic adverse drug reactions, cautious monitoring is crucial. (smw.ch)
- Hepatic drug metabolism and liver disease caused by drugs. (ufhealth.org)
- At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. (cdc.gov)
- Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. (medicotips.com)
Idiosyncratic drug-induced liver injury6
- Chen M, Borlak J, Tong W (2014) Predicting idiosyncratic drug-induced liver injury-some recent advances. (springer.com)
- Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. (uzh.ch)
- Idiosyncratic drug-induced liver injury: an update on the 2007 overview. (qxmd.com)
- Epidemiology of idiosyncratic drug-induced liver injury. (qxmd.com)
- Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study. (qxmd.com)
- Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals. (lsh.is)
- Three recent studies conducted by NIDDK's Drug-Induced Liver Injury Network (DILIN) have provided new insights into outcomes from this potentially severe form of liver injury, including the rate of fatal outcomes, frequency of bile duct damage and loss, and racial/ethnic disparities in disease severity. (nih.gov)
- The program is endorsed by the National Institutes of Health (NIH) Drug-induced Liver Injury Network (DILIN), the American Association for the Study of Liver Diseases (AASLD), the Hamner-UNC Institute for Drug Safety Sciences, and the Pharmaceutical Research and Manufacturers of America (PhRMA). (c-path.org)
- The staggering facts have prompted doctors and medical researchers to establish a vast, multi-center, ongoing study known as DILIN (Drug-Induced Liver Injury Network) to better understand why antibiotics and some other prescription drugs affect certain people so adversely. (antibioticliverdamage.com)
- Established in 2003 by The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Drug-Induced Liver Injury Network (DILIN) collects and analyzes cases of liver injury to help better understand their source. (dcri.org)
- According to Fontana, more than 1,600 patients have been enrolled into the study, and the DILIN team is now beginning to identify genetic markers in some patients who develop liver reactions. (uofmhealth.org)
- Indeed, genetic deficiencies in BSEP resulting in diminished or reduced BSEP activity or cell surface expression directly cause cholestatic liver diseases including progressive familial intrahepatic cholestasis type II (PFICII) and benign intrahepatic cholestasis (BRIC) or predispose to intrahepatic cholestasis of pregnancy and drug-induced cholestasis. (springer.com)
- Strautnieks SS, Bull LN, Knisely AS et al (1998) A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. (springer.com)
- Cholestatic injury refers to injury to the biliary system or to hepatocytes with resulting intrahepatic cholestasis. (unboundmedicine.com)
- For the first two years of my PhD, I focused on a particular type of liver injury called drug-induced cholestasis, which occurs when biliary transporters become inhibited by drugs and this leads to a toxic build-up of bile acids within liver cells. (liverpool.ac.uk)
- The predominant mechanism of drug-induced cholestasis is direct inhibition of BSEP, however in the following work, the contribution of BSEP repression on BSEP function was investigated. (umaryland.edu)
- Additional BSEP repressors were predicted from reported cases of drug-induced cholestasis combined with Bayesian modeling. (umaryland.edu)
- Metformin was used as a model drug in our studies, however, a number of drugs associated with cholestasis do not inhibit BSEP directly. (umaryland.edu)
- Overall, these results confirm BSEP repression represents an understudied mechanism for drug-induced cholestasis. (umaryland.edu)
- If symptoms are severe, you should rest and avoid heavy exercise, alcohol, acetaminophen, and any other substances that might harm the liver. (medlineplus.gov)
- This antituberculosis drug-induced liver injury (ATLI) ranges from a mild to severe form, and the associated mortality cases are not rare. (psu.edu)
- The drug isoniazid, rifampicin and pyrazinamide have the potential to induce liver damage.This anti-tuberculosis drug-induced liver injury (ATLI) ranges from mild to severe forms, and can even be fatal. (ukessays.com)
- N-acetylcysteine and prednisolone treatment improved serum biochemistries in suspected flupirtine cases of severe idiosyncratic liver injury. (semanticscholar.org)
- No patients met the criteria for severe drug-induced liver injury (Hy's Law) in the study. (thefreedictionary.com)
- Because the liver often fails to recognize some chemicals and chemical compounds, such as antibiotics and other prescription drugs, the organ can become damaged and in severe cases, stop performing when an antibiotic is introduced, much the way a car engine would sputter or even stop working if fed gasoline diluted with trace amounts of fruit juice. (antibioticliverdamage.com)
- Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, serum sickness, transfusion reactions. (drugs.com)
- Going forward, it is hoped that this line of research will lead to a reduction in adverse liver events from a multitude of drugs and herbal and dietary supplements, which are also increasingly associated with potentially severe liver reactions in some people. (uofmhealth.org)
- The pattern of liver injury is typically cholestatic or mixed, and it can be severe with serum bilirubin levels rising above 20 mg/dL. (nih.gov)
- Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. (cdc.gov)
- Liver failure and damage are rare but severe unintended consequences of statin drug use. (greenmedinfo.com)
- It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure. (medicotips.com)
- Severe injury may result in irretrievable loss of the function of an organ, massive hemorrhage, or shock. (thefreedictionary.com)
- Many drugs which cause infrequent but clinically severe liver injury (iDILI) in humans have been found to inhibit BSEP activity in vitro using a variety of different experimental model systems, and in vivo in experimental animals. (solvobiotech.com)
- Our study identified which medications put patients most at risk for developing liver diseases. (redorbit.com)
- Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). (lsh.is)
- Stopping the cannibalistic behavior of a well-studied enzyme could be the key to new drugs to fight age-related diseases, according to a new study published online in Nature Cell Biology. (news-medical.net)
- At the Mount Sinai Health System, our liver specialists or hepatologists have been at the forefront of groundbreaking advances in the detection and treatment of liver diseases for more than half a century. (mountsinai.org)
- For every 100 mg increase in intake of magnesium a 49% reduction in the risk for mortality due to liver diseases was found. (greenmedinfo.com)
- It includes traumatic brain injury and insults to the brain resulting from strokes, tumors, or neurological diseases such as multiple sclerosis. (thefreedictionary.com)
- Explores the role of autophagy in specific diseases and developments, including: Crohn's Disease, Gaucher Disease, Huntington's Disease, HCV infection, osteoarthritis, and liver injury, with a full section devoted to in-depth exploration of autophagy in tumor development and cancer, as well as the relationship between autophagy and apoptosis. (elsevier.com)
- Sherlock's Diseases of the Liver and Biliary System begins by introducing the anatomy and function of the liver to readers, continuing then with in-depth coverage of liver biopsy techniques and interpretation, and fibrogenesis and its assessment. (wiley.com)
- There are also chapters on the liver in pregnancy, in the neonate, infancy and childhood, in systemic diseases and in infections. (wiley.com)
- vascular diseases of the liver and portal vein thrombosis, and nutrition in liver disease. (wiley.com)
Adverse drug reac10
- 50%, with 37% of cases attributable to APAP and 13% attributable to idiosyncratic adverse drug reactions. (uspharmacist.com)
- The analysis was prompted by evidence from other studies of adverse drug reactions, such as the NIDDK-supported Acute Liver Failure Study Group, which found that African Americans were more at risk for acute liver failure from drugs than Caucasians. (nih.gov)
- In summary, the present work has led to an increased understanding of molecular properties important in ABC inhibition as well as the potential influence of ABC proteins in adverse drug reactions. (diva-portal.org)
- The ICSRs, drug-reaction pairs and adverse drug reactions were analysed descriptively, including a special focus on checkpoint inhibitors. (smw.ch)
- In total, 2042 ICSRs could be investigated, comprising 10,646 drugs and 6436 adverse drug reactions. (smw.ch)
- An average of three adverse drug reactions per ICSR were reported, most frequently including hepatocellular injury, cholestatic liver injury, and liver injury. (smw.ch)
- Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury. (semanticscholar.org)
- The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. (semanticscholar.org)
- Adverse drug reactions and organ damage: The liver. (lsh.is)
- Adverse drug reactions are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). (wikipedia.org)
- This is very important if you have liver disease. (medlineplus.gov)
- Sleisenger and Fordtran's Gastrointestinal and Liver Disease. (medlineplus.gov)
- This type of liver injury results from the use of certain prescription and over-the-counter medications, as well as dietary supplements, and is among the more challenging forms of liver disease due to its difficulty to predict, diagnose and manage. (redorbit.com)
- Teschke R, Eickhoff A (2016) The Honolulu liver disease cluster at the medical center: its mysteries and challenges. (springer.com)
- They further supported these findings by examining the frequency of the top three implicated genetic regions in 1319 disease-matched population controls who were not screened for abnormal liver test results. (medscape.com)
- Kullak-Ublick GA, Stieger B, Meier PJ (2004) Enterohepatic bile salt transporters in normal physiology and liver disease. (springer.com)
- When this point is reached, Krueger will then follow up by developing a genome expression profile for the proteins suspected of being involved in the disease to see which particular subset of regulated genes and pathways may be linked to susceptibility for drug-induced liver injury. (uconn.edu)
- One that requires a high degree of awareness of the condition and the careful exclusion of alternative aetiologies of liver disease. (easl.eu)
- The journal's aim is to publish articles focused on basic, clinic care and translational research that seeks to prevent rather than treat the complications of endstage liver disease. (elsevier.es)
- HLA-B*5701 and flucloxacillin associated drug-induced liver disease. (semanticscholar.org)
- Withholding statins in patients with underlying liver disease: wise or unwise? (thefreedictionary.com)
- The study, led by Prof Eric CHAN from the Department of Pharmacy, NUS was carried out using tacrine, an anti-Alzheimer's disease drug which may cause unintended liver damage. (nus.edu.sg)
- National nonprofit dedicated to the advocacy and promotion of education, support and research for the prevention and treatment of liver disease. (ucsd.edu)
- Information includes slide decks on specific types of liver disease, reports and links to abstracts of published articles. (ucsd.edu)
- She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. (cdc.gov)
- Our liver disease specialists evaluate the health and function of your liver, ensuring an expert diagnosis and a comprehensive treatment plan that can help stop and even reverse your liver disease. (mountsinai.org)
- Drug-induced liver injury is a cause of acute and chronic liver disease. (wikipedia.org)
- Acetaminophen (in the US and Japan), paracetamol (INN), also known by the brand name Tylenol and Panadol, is usually well tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and acute liver failure worldwide. (wikipedia.org)
- Celiac disease is found in a far higher percentage of patients with end-stage autoimmune liver disease. (greenmedinfo.com)
- Levothyroxine may be a risk factor for hypoglycaemia in patients with liver disease. (greenmedinfo.com)
- Patients with chronic liver disease have a high prevalence of anti-tTg antibodies, similar to patients with celiac disease. (greenmedinfo.com)
- Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis. (greenmedinfo.com)
- Effect of L-carnitine supplementation on lipid profiles of patients with liver disease. (greenmedinfo.com)
- This study determines the positive efficacy of vitamin D supplementation for chronic liver disease. (greenmedinfo.com)
- In addition to his expertise in medicinal chemistry, Bryan has significant cross functional drug discovery experience and expertise in additional disciplines, such as biomarkers, pharmacokinetic/pharmacodynamic (PK/PD) relationships, mechanisms of drug metabolism and toxicology. (complianceonline.com)
- Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment? (semanticscholar.org)
- MiR-122 and other microRNAs as potential circulating biomarkers of drug-induced liver injury. (semanticscholar.org)
- The search for biomarkers identifying an individual patient's risk of developing iDILI due to a given drug is impeded by the difficulty of iDILI diagnosis. (emjreviews.com)
- In order to provide proof-of-concept for a novel approach to the development of drug-specific iDILI biomarkers, a combination of monocyte-derived hepatocyte-like (MH) cells and proteomics was used. (emjreviews.com)
- With this information, physicians can better monitor and manage patients who are prescribed potentially liver-injuring drugs. (redorbit.com)
- Jaundice and other symptoms highly suggestive of liver injury, such as itching, nausea, abdominal discomfort and lethargy, were present in the majority of patients. (redorbit.com)
- Currently there is no method for clinicians to predict which patients with MS will experience this type of liver injury when treated with interferon-β. (medscape.com)
- They ran genetic testing in a separate cohort of 34 patients with MS from the United States and Sweden and found that 1q32.2 containing rs2205986 was the only region associated with interferon-β-induced liver injury. (medscape.com)
- The high rate of death among pediatric patients with antiepileptic-induced liver failure may relate to valproic acid-induced hyperammonemic encephalopathy and carnitine depletion, the investigators suggested. (medpagetoday.com)
- Our findings suggest that this therapy could be a clinically viable strategy for treating patients with drug-induced liver injury," says Suraj Patel, PhD, of the MGH Department of Surgery, the paper's lead author. (massgeneral.org)
- However, before we can think about applying this approach to patients, we need to know more about any off-target effects of these gap junction inhibitors and better understand the long-term ramifications of temporarily blocking liver-specific gap junction channels. (massgeneral.org)
- Patients and providers should be aware of this, as well as being aware of the potential for HDS to cause liver injury . (medicalxpress.com)
- The purpose of the study is to establish drug-induced liver injury databases in China, make criteria for Chinese drug-induced liver injury patients and evaluate the application of certain circulating miRNA in diagnosis or treatment of drug-induced liver injury. (clinicaltrials.gov)
- Otherwise,collect blood sample or other sample of the patients and study certain miRNA in diagnosis or treatment of drug-induced liver injury. (clinicaltrials.gov)
- Antiviral therapy with pegylated interferon and ribavirin for HCV in HCV-HIV coinfected patients is less successful than in patients with HCV monoinfection, and HAART can cause drug-induced liver injury. (nih.gov)
- Patients who develop ALF after taking these drugs typically do not experience a spontaneous recoverythe transplant-free survival rate in this study was 27 percent. (infectioncontroltoday.com)
- On average, patients used five drugs including two suspected drugs. (smw.ch)
- Drugs with potential for IDILI put the lives of patients at significant risk. (discoverx.com)
- Spontaneous resolution occurs in most patients but return to normal liver function may take months. (elsevier.com)
- Our findings suggest that this therapy could be a clinically viable strategy for treating patients with drug-induced liver injury ," said Suraj Patel, a postdoctoral researcher in the Center for Engineering in Medicine at MGH and the study's lead author. (thefreedictionary.com)
- Elevated liver enzymes in HIV monoinfected patients on HIV therapy: what are the implications? (thefreedictionary.com)
- 4] Twenty percent of patients develop asymptomatic elevation of liver enzymes which is self limiting (as a result of adaptation or discontinuance) in a majority of patients[ 4 , 5 , 6 , 7] but the outlook may be less favorable in those with develop jaundice, ascites, encephalopathy or acute liver failure. (tropicalgastro.com)
-  In another large series investigating acute liver failure in New Delhi, anti-TB drugs contributed to 5.7% patients with ALF(70/ 1223), with 67% mortality. (tropicalgastro.com)
- Patients should confer with their doctor when seeking an antibiotic prescription if they fear damaging their liver. (antibioticliverdamage.com)
- Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. (qxmd.com)
- For patients taking other enzyme-inducing AEDs (i.e., phenobarbital, phenytoin, and primidone ), higher doses of APTIOM may be needed [see DRUG INTERACTIONS ]. (rxlist.com)
- Are Liver Tests Needed in Pediatric Patients Receiving Statin Therapy? (gutsandgrowth.com)
- For instance, we're increasingly looking at whether patients' particular genes make them more susceptible to liver injury when taking certain drugs. (dcri.org)
- We are seeing more and more patients now with injuries due to supplements, and that trend has been growing over time," she said. (dcri.org)
- The frequency of these reactions varies between 1 in 10,000 patients taking the drug to less than 1 in a million. (uofmhealth.org)
- These drugs have been proven safe and effective for the vast majority of patients," Fontana says. (uofmhealth.org)
- However, as physicians, we should consider the possibility of liver damage in some patients and warn all patients of these risks … (and) also advise them of how to recognize the symptoms and what to do should they arise. (uofmhealth.org)
- This would allow marketing of innovative drugs by protecting patients at risk while granting access to the patients who tolerate the drug. (emjreviews.com)
- The misdiagnosis of other causes of liver injury as iDILI and, more importantly, unclear drug causality in cases of patients taking several drugs, leads to ill-defined patient sets for biomarker studies. (emjreviews.com)
- Patients who present with acute liver injury due to kratom usually recover rapidly once it is discontinued. (nih.gov)
- Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). (cdc.gov)
- These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH. (cdc.gov)
- Phase II trials of the first second-generation antisense cancer drug to be used in patients are soon to be underway in the wake of a successful Phase I study, which has demonstrated that the new drug blocks its target gene in exactly the way it is designed to do. (news-medical.net)
- Depression is a side-effect of efavirenz treatment in a minority of patients but its frequency has not been established in people receiving the drug in sub-Saharan Africa. (aidsmap.com)
- Under an IRB-approved protocol, serum and tissue samples are collected from patients who consent during clinic visits with the Liver Program. (unc.edu)
- Patients with liver injury at 6 months return for 12-, 36-, and 48-month visits. (umich.edu)
- Levothyroxine use is associated with increased risk of hypoglycemia in patients with liver impairment. (greenmedinfo.com)
- Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced liver injury is rare. (elsevier.com)
- The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent liver injury due to statins. (elsevier.com)
- Four patients developed chronic liver injury, of which three had an autoimmune phenotype of liver injury. (elsevier.com)
- Conclusion: Drug-induced liver injury from statins is rare and characterized by variable patterns of injury, a range of latencies to onset, autoimmune features in some cases, and persistent or chronic injury in 18% of patients, most of whom have an autoimmune phenotype. (elsevier.com)
- Chemical modifications can cause the drug to have both beneficial and adverse effects on patients. (phys.org)
- The researchers are currently developing a line of induced pluripotent stem cells or iPS cells, that are derived from skin and blood cells and can be turned into liver cells called hepatocytes. (uconn.edu)
- These are like pharmaceutically-naïve hepatocytes because they have never been exposed to pharmaceuticals in the liver. (uconn.edu)
- It includes key liver cell populations ( e.g. , hepatocytes, Kupffer cells), bile duct cells (cholangiocytes), intracellular biochemical systems ( e.g. , mitochondrial function), and whole body dynamics ( e.g. , drug distribution and metabolism). (simulations-plus.com)
- ALT, AST, ALP) from hepatocytes in the event of cell death, as well as increases in total bilirubin, reflecting compromised liver function due to hepatocyte loss. (simulations-plus.com)
- This conclusion was based upon research using rodent liver cells (hepatocytes) or in a cell line called HepG2 cells. (liverpool.ac.uk)
- After this surgical procedure, the liver is able to regenerate a new set of hepatocytes and regrow the lost portion of the organ. (lecturio.com)
- The dominant vitamins present in some of the hepatocytes in the liver are vitamin A, vitamin D , and vitamin B12 . (lecturio.com)
- In the following studies, human primary hepatocytes (HPH) were used predominantly as a physiologically relevant system for studying drug transporter function and expression upon drug treatment. (umaryland.edu)
- Impaired BSEP activity results in accumulation of bile acids within hepatocytes which can cause cholestatic liver injury. (solvobiotech.com)
- Thank you for sharing this Drug Metabolism & Disposition article. (aspetjournals.org)
- Message Body (Your Name) thought you would be interested in this article in Drug Metabolism & Disposition. (aspetjournals.org)
- The liver is the primary organ involved in the metabolism of carbohydrates, fats, and proteins. (lecturio.com)
- Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. (lsh.is)
- Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. (lsh.is)
- Taking advantage of a cancer cell's altered metabolism that drives its runaway growth, Princess Margaret researchers are zeroing in on these molecular changes to help them develop more precise drug targets for one of the most deadly breast cancers. (news-medical.net)
- Chronic use of kratom recreationally has been associated with rare instances of acute liver injury. (nih.gov)
- An estimated 2 billion people worldwide have been infected with HBV and about 400 million persons are living with chronic HBV infection. (unc.edu)
- The dose toxic to the liver is quite variable from person to person and is often thought to be lower in chronic alcoholics. (wikipedia.org)
- Liver enzymes will be higher if you have the condition. (medlineplus.gov)
- The new multi-donor microtissues offer the same structural and functional robustness of single-donor microtissues, but provide a more diverse genetic background to help mitigate bias in models resulting from naturally occurring variations in drug-metabolizing Cytochrome P450 enzymes. (technologynetworks.com)
- Pharmaceutical drugs are broken down by enzymes in the liver into their metabolites, which are subsequently excreted in the faeces and urine. (nus.edu.sg)
-  Damage to the liver is not due to the drug itself but to a toxic metabolite ( N -acetyl- p -benzoquinone imine (NAPQI)) produced by cytochrome P-450 enzymes in the liver. (wikipedia.org)
- Gerloff T, Stieger B, Hagenbuch B et al (1998) The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. (springer.com)
- Another Network-driven study focused on one particular pattern of injury from drug-induced liver injury in which the bile ducts are damaged or even lost in a condition called vanishing bile duct syndrome. (nih.gov)
- They analyzed liver biopsies that had been obtained from some of the participants sometime in the decade following their injury and scored the biopsies for bile duct loss. (nih.gov)
- The researchers identified some of the drugs or supplements most commonly associated with the bile duct injury, including specific antibiotics and herbal supplements. (nih.gov)
- Also they can result in organelle stress (e.g. mitochondrial or endoplasmic reticulum (ER)stress), interfere with bile acid transport and either lead to lethal consequences (necrosis or apoptosis) or induce adaptive responses. (easl.eu)
- The mechanisms currently included are: (1) inhibition of bile acid transporters leading to disruptions in bile acid homeostasis, (2) alteration of mitochondrial function , (3) generation of oxidative stress , and (4) cholestatic injury to bile duct cells via disruption in the ratio between phospholipids and bile acids in the bile. (simulations-plus.com)
- A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. (ovid.com)
- Transporter inhibition by TAK-875 may cause liver injury in dogs through altered bile BA composition characteristics, as evidenced by crystalline deposition, likely composed of test article, in the bile duct. (ovid.com)
- ABCB11) dictating excretion of bile acids from the liver to the gall bladder. (umaryland.edu)
- One of the antibiotics the research team is focusing on is isoniazid, which is used worldwide to treat tuberculosis and causes drug-induced liver injury in about 1 percent of all people who take the drug. (uconn.edu)
- DOTS is a short course of standard anti-TB treatment which consist of taking drug combinations of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol and Streptomycin for 6-9 months. (ukessays.com)
- Always tell your provider about all the medicines you take, including over-the-counter drugs and herbal or supplemental preparations. (medlineplus.gov)
- It can occur with use of over-the-counter or prescription drugs, as well as with herbal or dietary supplements. (nih.gov)
- The Network was formed in 2003 to understand how drugs or herbal/dietary supplements cause liver injury and to determine long-term outcomes following this injury. (nih.gov)
- A panel of experts reviews each case to determine whether the injury was likely caused by the drug or herbal/dietary supplement, as well as the severity of the injury. (nih.gov)
- In addition, subjects with liver injury due to herbal products are eligible to participate. (qxmd.com)
- Herbal and Dietary Supplement-Induced Liver Injury. (semanticscholar.org)
- should we worry about liver inflammation? (nih.gov)
- A new liver biopsy showed portal inflammation with eosinophils and a METAVIR A1 F2. (hindawi.com)
- Recent work by the MGH team and others has shown that assemblies of intercellular gap junctions spread immune signals from injured liver cells to surrounding undamaged cells, amplifying overall inflammation and injury. (massgeneral.org)
- Compared to normal mice, those lacking liver gap junctions were protected against liver damage, inflammation and death caused by administration of liver-toxic drugs. (massgeneral.org)
- Growing evidence underlines a pathogenic contribution of sterile postinjury inflammation in APAP-induced acute liver injury (APAP-ALI) and justifies development of anti-inflammatory therapies with therapeutic efficacy beyond the therapeutic window of the only current treatment option, N-acetylcysteine (NAC). (ovid.com)
- 2G7 treatments significantly attenuated APAP-induced serum elevations of alanine aminotransferase and microRNA-122 and completely abrogated markers of APAP-induced inflammation (tumor necrosis factor, monocyte chemoattractant protein 1, and chemokine [C-X-C motif] ligand 1) with prolonged therapeutic efficacy as compared to NAC. (ovid.com)
Acute liver injury2
- Jaundice, a yellowish discoloration of the skin, is typically one of the first and most common signs of liver damage, or hepatoxicity. (antibioticliverdamage.com)
- The onset of injury is usually within 2 to 8 weeks of starting regular use of kratom powder or tablets, with symptoms of fatigue, nausea, pruritus and dark urine followed by jaundice. (nih.gov)
- Additionally, cell culture experiments indicated that blocking gap junctions limited the spread through liver cells of damaging free radicals and oxidative stress, suggesting a possible mechanism for the observed protection. (massgeneral.org)
- They can covalently bind to proteins, induce oxidative stress, activate signal transduction pathways (e.g. mitogen-activated protein (MAP) kinases). (easl.eu)
Acetaminophen-induced liver injury2
- acetylcysteine for acetaminophen-induced liver injury. (uspharmacist.com)
- An example that highlights this potential problem is found in a recent report demonstrating a pathogenic role for natural killer T (NKT) and natural killer (NK) cells in acetaminophen-induced liver injury (AILI) in C57Bl/6 mice in which DMSO was used to facilitate acetaminophen (APAP) dissolution. (wiley.com)
- Drugs or compounds inhibiting BSEP activity, repressing BSEP transcription, or reducing cell surface expression of BSEP protein have the potential to induce cholestatic liver injury. (springer.com)
- In their report receiving advance online publication in the journal Nature Biotechnology , the team reports that inhibition of a type of cell-to-cell communication can protect against the damage caused by liver-toxic drugs such as acetaminophen. (massgeneral.org)
- This study aimed to characterize the relationship between MRP3, MRP4, and BSEP inhibition and cholestatic potential of drugs. (sigmaaldrich.com)
- In conclusion, a combination of in vitro and in vivo evidence suggests that BA transporter inhibition could contribute to TAK-875-mediated liver injury in dogs. (ovid.com)
- BSEP inhibition is one of several adverse properties which appear to play important roles in initiation of iDILI, therefore screening for in vitro BSEP inhibition is likely to be of greatest value if undertaken alongside screening for other relevant adverse effects (e.g. mitochondrial injury, cell cytotoxicity, metabolic bioactivation). (solvobiotech.com)
- Sarges P, Steinberg JM, Lewis JH (2016) Drug-induced liver injury: highlights from a review of the 2015 literature. (springer.com)
- Danan G, Teschke R (2016) RUCAM in drug and herb induced liver injury: the update. (springer.com)
- Hayashi PH (2016) Drug-induced Liver Injury Network causality assessment: criteria and experience in the United States. (springer.com)
- Douros A, Bronder E, Andersohn F, Klimpel A, Kreutz R, Garbe E, Bolbrinker J (2016) Herb-induced liver injury in the Berlin Case-Control Surveillance Study. (springer.com)
- 2016. https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602267/all/Drug_Induced_Liver_Injury. (unboundmedicine.com)
- 2016) Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury? (systembio.com)
- Hepatocellular injury refers to injury to the liver cell. (unboundmedicine.com)
- Mixed hepatocellular and cholestatic injury refers to injury to both. (unboundmedicine.com)
- Components of the signature include the typical latency from the onset of treatment, whether there are extrahepatic manifestations, whether the injury is hepatocellular, cholestatic or mixed, and sometimes characteristic features on biopsy or serological testing (e.g. liver autoantibodies). (unboundmedicine.com)
- The pattern of injury was hepatocellular in all. (elsevier.com)
- A HCC derived human hepato-carcinoma cell line (ATCC No. HB-8065) from liver tissue of a 15 year old Caucasian American male with a well differentiated hepatocellular carcinoma. (mipdili.eu)
- Hepatocellular carcinoma, angiosarcoma and liver adenomas are the ones usually reported. (medicotips.com)
Medication-Induced Liver Injury1
- Preliminary Results of a Novel Algorithmic Method Aiming to Support Initial Causality Assessment of Routine Pharmacovigilance Case Reports for Medication-Induced Liver Injury: The PV-RUCAM. (semanticscholar.org)
- Chen M, Borlak J, Tong W (2013) High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. (springer.com)
- They also observed that drug-induced liver failure, while a rare event, "has wide implications for all of us who take and prescribe medications," and that in coming years significant advances can be expected in understanding of factors such as genetic predisposition. (medpagetoday.com)
- LiverTox includes an overview of medications (their chemical nature, indications, recommended dosages, and frequency of use), a description of the pattern and course of liver injury, case histories with laboratory data, and a comprehensive list of references. (uspharmacist.com)
- The frequency at which these medications are prescribed means that kidney and liver toxicities are quite common. (nurse.com)
- Drug-induced liver injury is a potential complication of many medications because the liver is central to the metabolic disposition of most drugs. (thefreedictionary.com)
- Knowledge of some features of the liver makes it easier to understand the signs and symptoms caused by medications in case of toxicities. (lecturio.com)
- Some medications and supplements can damage your liver. (ucsd.edu)
- The goal of this multicenter NIH study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications (CAM) within 6 months of onset. (umich.edu)
Cases of drug-induced liver injury2
- Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 inhabitants, per year. (redorbit.com)
- Among 1,188 cases of drug-induced liver injury enrolled between 2004 and 2012 in a prospective registry by the U.S. Drug Induced Liver Injury Network, 22 were attributed to a statin. (elsevier.com)
- In both types the chemical characteristics of the drug are important, particularly lipophilicity and drug biotransformation. (easl.eu)
- In this thesis, drug-transport protein interactions were explored using large, diverse datasets representing the chemical space of orally administered registered drugs. (diva-portal.org)
- Drugs can also undergo chemical reactions mediated by bacteria within the gut, an important process that is commonly neglected. (nus.edu.sg)
- Running chemical analyses on these products now is helping to reveal illegal and potentially dangerous drugs not on the label. (dcri.org)
- As part of the Critical Assessment of Massive Data Analysis (CAMDA) "CMap Drug Safety Challenge" 2019 ( http://camda2019.bioinf.jku.at ), chemical structure-based models were generated using the binarized DILIrank annotations. (beds.ac.uk)
- NUS pharmaceutical scientists have discovered the mechanisms involved when small chemical modifications to certain pharmaceutical drugs may cause harm instead of improving treatment. (phys.org)
- The process of drug design to improve therapeutic activities involves making small chemical changes to drug molecules. (phys.org)
- Using in vitro experiments with human liver cells , the team found that minor chemical modifications can affect the stability of drug compounds as these alter the generation of reactive metabolites. (phys.org)
- Prof Ho Han Kiat with his research team investigating the mechanisms involved when small chemical modifications are made to pharmaceutical drugs. (phys.org)
- Prof Ho said, "The research findings show that it is important to examine the potential toxicological impact when making minor chemical changes to pharmaceutical drugs . (phys.org)
- It offers a structured, standardized diagnostic approach specific to liver injury by attributing scores to individual key items that provide final quantitative gradings of causality. (springer.com)
- The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. (semanticscholar.org)
- Agreement Among Different Scales for Causality Assessment in Drug-Induced Liver Injury. (semanticscholar.org)
- The latency to onset of liver injury ranged from 34 days to 10 years (median=155 days). (elsevier.com)
- A 21-year-old male patient with drug-induced liver injury visited the clinic five times from January 28th, 2019 to March 16th, 2019. (jikm.or.kr)
- The study also showed that drug-induced liver injury was caused by a single prescription medication in 75 percent of cases, by dietary supplements in 16 percent and by multiple agents in 9 percent. (redorbit.com)
- Now that progression of HIV and deaths due to AIDS can be prevented by highly active antiretroviral therapy (HAART), it is clear that HCV coinfection is associated with accelerated progression to cirrhosis and increased liver-related morbidity and mortality. (nih.gov)
- Our findings highlight the importance for healthcare providers in Switzerland to pay special attention to possible drug-induced liver injuries because of their high mortality rate. (smw.ch)
- As a pioneer in the drug transporter field for 20 years, SOLVO is dedicated to exploring the science of transporters and their role in xenobiotic efficacy and safety. (solvobiotech.com)
- Recently, BSEP has been highlighted by the International Transporter Consortium as one of the emerging transporters which need to be considered when evaluating drug safety. (solvobiotech.com)
- But for some individuals, treatment with certain antibiotics can bring on a new set of health problems, including serious liver damage. (uconn.edu)
- While all antibiotics can cause liver failure, certain types are generally known to be more risky than others. (antibioticliverdamage.com)
- One antibiotic, currently under attack by many legislators, medical experts, and consumer safety advocates, has shown to cause drug-induced liver injury four times more frequently than other antibiotics, even after less than 10 doses. (antibioticliverdamage.com)
- Antibiotics and Liver Injury: What's the Relationship and Risk? (uofmhealth.org)
- And it is one of many on a long list of antibiotics associated with liver-related adverse events. (uofmhealth.org)
- Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. (tropicalgastro.com)
- and initiation of a systemic hypersensitivity response (i.e., drug allergy) that damages the liver. (uspharmacist.com)
- Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. (semanticscholar.org)
- Drug-induced T-cell mediated hypersensitivity reactions are feared by clinicians and pharmaceutical companies alike. (biomedcentral.com)
- Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. (semanticscholar.org)
- Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication. (mipdili.eu)
- A rash or fever may be part of some drug reactions that affect the liver. (medlineplus.gov)
- In MS…the mechanisms by which the biologics work to prevent disability are relatively unknown and this makes it even harder to predict what type of drugs reactions will occur and in whom," said Kowalec, who is now a postdoctoral research at Karolinska Institutet in Stockholm, Sweden. (medscape.com)
- Both of these mechanisms highlight that the unique interaction between drug, T-cell receptor and MHC molecule is a key factor in the development of immune-mediated adverse reactions to drugs and, as such, the study of HLA alleles represents a logical route to study the genetic basis of such immune-mediated reactions. (biomedcentral.com)
- In early drug discovery, in silico models can be used as predictive filters in the drug candidate selection process and membrane vesicles as a first experimental screening tool to investigate protein interactions. (diva-portal.org)
- However, carbamazepine reduces the plasma concentration of eslicarbazepine [see DRUG INTERACTIONS ]. (rxlist.com)
- Drug-induced liver injury: Interactions between drug properties and host factors. (lsh.is)
- Currently, a number of in vitro methods are employed to assess the cholestatic potentials of drugs or compounds. (springer.com)
- The findings from this work suggest a novel drug development strategy in which therapeutically effective but potentially liver-toxic compounds could be co-formulated with selective gap junction inhibitors to improve their safety," explains Patel, a co-founder of Heprotech along with Yarmush. (massgeneral.org)
- DILIsym also supports key management decisions about compounds for which liver transaminase elevations have already been observed by identifying patient screening or dosing protocols to mitigate risk. (simulations-plus.com)
- The structures of all compounds in the test and training sets as well as the set of recently approved drugs are available in sdf format online, and the Bayesian model protocols used in Discovery Studio are available from the authors upon request. (aspetjournals.org)
- Drug-induced liver injury: an overview over the most critical compounds. (qxmd.com)
- Several groups of researchers have proposed that pro-active in vitro screening for BSEP during drug discovery may aid in early flagging and deselection of compounds which have high propensity to cause iDILI. (solvobiotech.com)
- The compounds were tested in human liver cells, and also with and without the presence of glutathione (GSH, an anti-oxidant), in human liver microsomes (HLMs). (phys.org)