Drug-Induced Liver Injury: 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.Drug-Induced Liver Injury, Chronic: Liver disease lasting six months or more, caused by an adverse drug effect. The adverse effect may result from a direct toxic effect of a drug or metabolite, or an idiosyncratic response to a drug or metabolite.Liver Diseases: Pathological processes of the LIVER.Drug-Related Side Effects and Adverse Reactions: Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.Liver Function Tests: Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. It conducts and supports basic and applied research for a national program in diabetes, endocrinology, and metabolic diseases; digestive diseases and nutrition; and kidney, urologic, and hematologic diseases. It was established in 1948.Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.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.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.Hepatitis E: Acute INFLAMMATION of the LIVER in humans; caused by HEPATITIS E VIRUS, a non-enveloped single-stranded RNA virus. Similar to HEPATITIS A, its incubation period is 15-60 days and is enterically transmitted, usually by fecal-oral transmission.Hepatitis E virus: A positive-stranded RNA virus species in the genus HEPEVIRUS, causing enterically-transmitted non-A, non-B hepatitis (HEPATITIS E).Necrosis: 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.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Wounds and Injuries: Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another.Retrospective Studies: 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.Liver Regeneration: Repair or renewal of hepatic tissue.Liver Neoplasms: Tumors or cancer of the LIVER.Brain 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.Reperfusion Injury: Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.Fatty Liver: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.Liver Diseases, Alcoholic: Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.

*  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. ...

*  DILIN's Prospective Study - Full Text View - ClinicalTrials.gov

Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014 Oct;60(4): ... Cholestatic Liver Injury. Hepatocellular Liver Injury. Mixed Liver Injury. Matched Case Control Studies. Genotype. Liver Dis. ... US Drug-Induced Liver Injury Network. Liver injury from tumor necrosis factor-α antagonists: analysis of thirty-four cases. ... Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced ...

*  Neil Kaplowitz, | Keck School of Medicine of USC

Drug Saf. 2007; 30(4):277-94. View in: PubMed. Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in ... Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to ... Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017 Oct; 66(4):1275-1285. ... Mechanisms of drug-induced liver injury. Clin Liver Dis. 2013 Nov; 17(4):507-18, vii. View in: PubMed ...

*  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 Doesn't? Why? ...

*  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. ... Hepatotoxicity Drug-induced liver injury Fulminant hepatic failure Abbreviations. A-DILI. Acetaminophen drug-induced liver ... Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 10:1018-1023 ... Objective To review all cases of drug-induced liver injury (DILI) requiring hospitalization at a single tertiary care center. ...

*  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 ...

*  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. ...

*  Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters...

Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug ... Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters ... of cholestatic drugs inhibited MRP4 (P < 0.05); in contrast, only 17% of non-cholestatic drugs were MRP4 inhibitors. Among BSEP ... In this group, for each 1% increase in MRP4 inhibition, the odds of the drug being cholestatic increased by 3.1%. Using an ...

*  AID 625280 - Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for...

Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis. ...

*  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 ...

*  AASLD - Topics: Drug-induced liver injury, Environmental toxins

Liver Injury/Regeneration Free Peroxisome proliferator‐activated receptor‐β/δ protects against chemically induced liver ... Original Article Free IL‐10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in ... Liver Biology and Pathobiology‐‐‐Pathobiology Free Diverse regulation of NF‐κB and peroxisome proliferator‐activated receptors ... Original Article Free Arsenic stimulates sinusoidal endothelial cell capillarization and vessel remodeling in mouse liver ...

*  AASLD - Topics: Drug-induced liver injury, Specific drug effects

Liver Injury/Regeneration Free Liver injury from herbals and dietary supplements in the U.S. DrugInduced Liver Injury Network ... Liver histology in the diagnosis and prognosis of druginduced liver injury Authors:. David E. Kleiner. Clinical Liver Disease ... Editorial Free Halothane‐induced hepatitis: Paradigm or paradox for druginduced liver injury Authors:. Mark J Kurth, Tsuyoshi ... RemoveDrug-induced liver injury * RemoveSpecific drug effects *show more (-7) ...

*  Aptiom (Eslicarbazepine Acetate Tablets): Side Effects, Interactions, Warning, Dosage & Uses

... drug interactions, warnings, patient labeling, reviews, and related medications. ... Drug Induced Liver Injury. Hepatic effects, ranging from mild to moderate elevations in transaminases (,3 times the upper limit ... Liver problems. APTIOM may affect your liver. Symptoms of liver problems include: *yellowing of your skin or the whites of your ... Drug addiction, which develops after repeated drug abuse, is characterized by a strong desire to take a drug despite harmful ...

*  Needle-stick injury | definition of needle-stick injury by Medical dictionary

What is needle-stick injury? Meaning of needle-stick injury medical term. What does needle-stick injury mean? ... Looking for online definition of needle-stick injury in the Medical Dictionary? needle-stick injury explanation free. ... drug-induced liver injury. Abbreviation: DILI.. Hepatic inflammation, hepatocellular necrosis, or jaundice due to exposure to a ... birth injury. Injury sustained by the neonate during birth. blast injury. An injury due to an explosion. The injury results ...

*  ADMET : Pharmaceuticals : All

9:45 Deciphering the mechanism of drug-induced liver injury (DILI) of Cinchophen. ... drug disposition and drug-induced liver toxicity. In 2000, Andreas joined Schering AG in Berlin where he helped setting up and ... drug disposition and drug-induced liver toxicity. In 2000, Andreas joined Schering AG in Berlin where he helped setting up and ... drug-drug interaction predictions and mechanistic understanding of the clinically occurring drug-drug interactions; transporter ...

*  Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the...

AILI, acetaminophen-induced liver injury; APAP, acetaminophen; DILI, drug-induced liver injury; DMSO, dimethyl sulfoxide; IFN-γ ... Immunological mechanisms of drug-induced liver injury. Curr Opin Drug Discov Dev 2005; 8: 38-43.. *PubMed , ... Drug-induced liver injury (DILI) is a serious, often fatal side effect of drug treatment representing a major impediment to ... Mechanisms of drug-induced liver disease. Clin Liver Dis 2007; 11: 459-475, v.. *CrossRef , ...

*  Eslicarbazepine Acetate Monograph for Professionals - Drugs.com

Drug-induced Liver Injury. Adverse hepatic effects, ranging from mild to moderate transaminase elevations (,3 times the ULN) to ... HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review. Clin Pharmacol Ther. 2012; 92:757 ... Drugs.com Mobile Apps. The easiest way to lookup drug information, identify pills, check interactions and set up your own ... Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and ...

*  Current Funding Opportunities | NIDDK

Limited Competition for the Continuation of the Drug Induced Liver Injury Network (DILIN) Clinical Centers (U01). Summary ... Limited Competition for the Continuation of the Drug Induced Liver Injury Network Data Coordinating Center (U24). Summary ...

*  Wiley: Sherlock's Diseases of the Liver and Biliary System, 12th Edition - James S. Dooley, Anna Lok, Andrew K. Burroughs, et al

24 Drug-Induced Liver Injury, 478. Leonard B. Seeff & Robert J. Fontana ... Clinical and biochemical presentations of drug-induced liver disease, 488. Assessment of suspected drug-induced liver disease, ... Predictors of susceptibility and outcome in druginduced liver injury, 483. Mechanisms of injury, drug metabolism and ... Diagnostic approaches and causality assessment of drug-induced liver injury, 487. ...

*  RNA-Based New Technique Opens Possibilities For Development Of New Antimicrobials

Anti-microbials Cause Drug-induced Liver Injury and Failure. Anti-microbial medications are a common cause of drug-induced ... Candidate Drug may Heal Injuries Without Blood Clots DNA of Victims Provide Cause of Sixteenth-Century Epidemic Genes that aid ... liver injury (DILI) leading to acute liver failure (ALF), with women and minorities severely affected, reports a ten-year study ... E.Coli Antimicrobial Resistance Increased by Five Times for Commonly Used UTI Drug. Antimicrobial resistance to one of the most ...

*  General Terms | Adult and Adolescent ARV | AIDSinfo

drug-induced liver injury. DMPA. depot medroxyprogesterone acetate. DOT. directly observed therapy. ... Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. *Home ...

*  Preliminary Evaluation of a Point-Of-Care Liver Function Test - Full Text View - ClinicalTrials.gov

HIV Tuberculosis Drug-Induced Liver Injury Device: Diagnostics for All liver function test (LFT) ... Chemical and Drug Induced Liver Injury. Mycobacterium Infections. Actinomycetales Infections. Gram-Positive Bacterial ... Liver Diseases. Digestive System Diseases. Drug-Related Side Effects and Adverse Reactions. Chemically-Induced Disorders. ... Preliminary Evaluation of a Point-Of-Care Liver Function Test (DFA). This study has been completed. ...

*  Entocort - for how long? - Crohn's Disease - HealingWell.com Forum

July 2007 Drug-Induced Liver Injury. January 2008 Crohn's Ileitis. Currently trying.... Enteral Nutrition, Flax Oil, VSL#3, ... That's when I had to go on the evil drug Prednisone. I wish you success. It's a great drug when it works. Crohn's Disease. ... recently dxed as drug induced 2008 Crohns Disease 1996,Hypothyroidism 1998, Raynauds 2006, Sjogrens 2008, Lupus 2008, Chronic ... I live in Canada and it is expensive, but less so than the US. I pay $100 for 60 tabs (it has gone down in price). I'm sure you ...

*  Anyone with Entocort experiences? - Crohn's Disease - HealingWell.com Forum

July 2007 Drug-Induced Liver Injury. January 2008 Crohn's Ileitis. Currently trying... ... Been living with Crohn's Disease for 32 years. Currently on Asacol, Prilosec 60 mg, Estrace, Prinivil, Diltiazem, Percoset prn ... I would appreciate any feedback you may have on this drug - good or bad. ...

*  PureCajunSunshine: May 2009

HOW TO COOK AND LIVE LIKE A REAL CAJUN - Jazz Up Your Kitchen Without Setting Your Mouth on Fire. *---> Jambalaya-ya-ya ... Elderberry is considered by many herbalists and satisfied users to be nature's answer to Tamiflu, a drug that is commonly used ... No one really knows what elderberry preparations will do in the face of an influenza induced cytokine storm.. Experts agree ... The unexpected can befall anyone: illness, accidents, serious injury, unemployment, fire... the list is long and is an equal- ...

American Association for the Study of Liver Diseases: The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists (including Hans Popper, Leon Schiff, Fred Hoffbauer, Cecil Watson, Jesse Bollman, and Sheila Sherlock, to name a few) to bring together those who had contributed to the field of hepatology.Idiosyncratic drug reactionLiver biopsyRumack-Matthew nomogram: The Rumack-Matthew nomogram, also known as Rumack-Matthews nomogram or the Acetaminophen nomogram is an acetaminophen toxicity nomogram plotting serum concentration of acetaminophen against the time since ingestion in an attempt to prognosticate possible liver toxicity as well as allowing a clinician to decide whether to proceed with N-Acetylcysteine (NAC) treatment or not. It is a logarithmic graph starting not directly from ingestion, but from 4 hours post ingestion after absorption is considered likely to be complete.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GIAlanine transaminase: Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALAT) and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT).King's College Criteria: The King's College Criteria or the King's College Hospital criteria were devised in 1989 to determine if there were any early indices of poor prognosis in patients with acute liver failure. Acute liver failure is defined as the onset of encephalopathy (altered mental status) or coagulopathy (altered bleeding tendencies) within 26 weeks of a patient diagnosed with liver disease.TransaminaseHepatitis E virus cis-reactive elementCoagulative necrosis: Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction. In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days.Prescription cascade: Prescription cascade refers to the process whereby the side effects of drugs are misdiagnosed as symptoms of another problem resulting in further prescriptions and further side effects and unanticipated drug interactions. This may lead to further misdiagnoses and further symptoms.National Center for Injury Prevention and Control: The U.S.QRISK: QRISK2 (the most recent version of QRISK) is a prediction algorithm for cardiovascular disease (CVD) that uses traditional risk factors (age, systolic blood pressure, smoking status and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with body mass index, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.Mir-652 microRNA precursor family: In molecular biology mir-652 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, with expression levels of miRNAs and respective target mRNAs negatively correlated.Jean Emond: Jean C. Emond is the current Thomas S.Metastatic liver disease: A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. The liver is a common site for metastatic disease because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein).Brain injury: A brain injury is any injury occurring in the brain of a living organism. Brain injuries can be classified along several dimensions.Fatty liverFibroTest: FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy.

(1/2195) Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease.

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)

(2/2195) Structural and functional changes in acute liver injury.

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)

(3/2195) Various forms of chemically induced liver injury and their detection by diagnostic procedures.

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)

(4/2195) Quantitative aspects in the assessment of liver injury.

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)

(5/2195) Assessment of hepatotoxic potential.

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)

(6/2195) Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro.

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)

(7/2195) Effect of central corticotropin-releasing factor on carbon tetrachloride-induced acute liver injury in rats.

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)

(8/2195) Influences of Kupffer cell stimulation and suppression on immunological liver injury in mice.

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)



DILI

  • 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)
  • Objective To review all cases of drug-induced liver injury (DILI) requiring hospitalization at a single tertiary care center. (springer.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). (springer.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)
  • Anti-microbial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure (ALF), with women and minorities severely affected, reports a ten-year study. (medindia.net)
  • 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 that causes hepatocellular injury (not cholestatic injury) with jaundice. (wikipedia.org)
  • Other medical areas where prognostic indicators are used is in Drug-Induced Liver Injury (DILI) (Hy's law) and use of an exercise stress test as a prognostic indicator after myocardial infarction, also use to indicator multiple myeloma survive rate. (wikipedia.org)

hepatic

  • 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)
  • Bjornsson E, Jerlstad P, Bergqvist A, Olsson R (2005) Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. (springer.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)
  • Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. (wikipedia.org)
  • Fulminant hepatitis, or massive hepatic cell death, is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B, D, and E, in addition to drug-induced and autoimmune hepatitis. (wikipedia.org)

hepatotoxicity

  • 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. (springer.com)
  • Among Phase I CYP450 enzymes, the subfamilies CYP2D6 and CYP3A are responsible for hepatotoxicity during drug metabolism with a number of different drugs, including flucloxacilin, trioleandomycin, and troglitazone. (wikipedia.org)
  • Hepatotoxicity indicates the drug's toxicity to liver. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Although individual analgesics rarely induce liver damage due to their widespread use, NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. (wikipedia.org)
  • it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients. (wikipedia.org)
  • Jay Houston Hoofnagle is an American M.D. He is a leading expert in hepatotoxicity, hepatitis, cirrhosis and other diseases of the liver, and director of the Liver Disease Research Branch in the Division of Digestive Diseases and Nutrition at the National Institutes of Health. (wikipedia.org)

Acetaminophen

  • acetylcysteine for acetaminophen-induced liver injury. (uspharmacist.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)
  • The mice were administered various liver-toxic drugs, such as the commonly used medicine acetaminophen. (massgeneral.org)
  • Overdoses of acetaminophen, which is best known under the brand name Tylenol, are the most frequent cause of drug-induced liver injury. (massgeneral.org)
  • 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)
  • As in the case of acetaminophen overdose, this type of injury occurs shortly after some threshold for toxicity is reached. (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)

transplantation

  • 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)
  • two further participants required liver transplantation. (wikipedia.org)
  • 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)

idiosyncratic

  • 50%, with 37% of cases attributable to APAP and 13% attributable to idiosyncratic adverse drug reactions. (uspharmacist.com)
  • Adverse drug reactions are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). (wikipedia.org)

hepatitis

  • 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)
  • No other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injury. (wikipedia.org)
  • Overconsumption can lead to toxicity-induced hepatitis. (wikipedia.org)
  • Severe liver damage and hepatitis has also been associated with bentazepam. (wikipedia.org)
  • Hepatitis is inflammation of the liver tissue. (wikipedia.org)
  • Acute hepatitis can sometimes resolve on its own, progress to chronic hepatitis, or rarely result in acute liver failure. (wikipedia.org)
  • Both hepatitis B and hepatitis C are commonly spread through infected blood such as may occur during needle sharing by intravenous drug users. (wikipedia.org)
  • Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer. (wikipedia.org)
  • Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. (wikipedia.org)
  • Chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ. (wikipedia.org)
  • Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools. (wikipedia.org)
  • The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. (wikipedia.org)
  • Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. (wikipedia.org)
  • Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity. (wikipedia.org)
  • Before joining the NIH, he was a senior scientist at the Hepatitis Branch, Division of Blood and Blood Products, Food and Drug Administration. (wikipedia.org)

pluripotent

  • Cellular Dynamics International (CDI) is a large scale manufacturer of human cells, created from induced pluripotent stem cells, for use in basic research, drug discovery and regenerative medicine applications. (wikipedia.org)
  • In a developing embryo, stem cells can differentiate into all the specialized cells-ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)-but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. (wikipedia.org)

AASLD

  • 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)

LiverTox

  • 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)
  • More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. (wikipedia.org)
  • In this capacity, Hoofnagle oversees the Drug-Induced Liver Injury Network and LiverTox, a database that provides "comprehensive and unbiased information about drug induced liver injury caused by prescription and nonprescription drugs, herbal and dietary supplements. (wikipedia.org)
  • Livertox: Clinical and Research Information on Drug-Induced Liver Injury (2014) "Drug Record: Sevoflurane", U.S. National Library of Medicine, 2 July 2014 update, see , accessed 15 August 2014. (wikipedia.org)

phenytoin

  • 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)
  • Other CYP-inducing anticonvulsants (e.g., phenobarbital, phenytoin, primidone): Higher dosages of eslicarbazepine acetate may be necessary (see Specific Drugs under Interactions). (drugs.com)

efficacy and tolerability

  • Carbamazepine: Dosages of eslicarbazepine acetate and/or carbamazepine may require adjustment based on efficacy and tolerability (see Specific Drugs under Interactions). (drugs.com)

cytochrome

  • As a drug that induces cytochrome P450 enzymes, it accelerates elimination of many benzodiazepines and decreases their action. (wikipedia.org)
  • 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)

clinically

  • 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)

cholestatic

  • This study aimed to characterize the relationship between MRP3, MRP4, and BSEP inhibition and cholestatic potential of drugs. (sigmaaldrich.com)
  • in contrast, only 17% of non-cholestatic drugs were MRP4 inhibitors. (sigmaaldrich.com)

severe

  • Severe injury may result in irretrievable loss of the function of an organ, massive hemorrhage, or shock. (thefreedictionary.com)

mice

  • The researchers first used a strain of genetically mutated mice that lack a particular liver-specific gap junction. (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)
  • The team then identified a small-molecule inhibitor of liver gap junctions that, when given with or even after the toxic drugs, protected the livers of normal mice against any injury and prevented their death. (massgeneral.org)

disease

  • Ibanez L, Perez E, Vidal X, Laporte JR, the Grup d'Estudi Multicentric d'Hepatotoxicitat Aguda de Barcelona (GEMHAB) (2002) Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: epidemiological and clinical features, and exposure to drugs. (springer.com)
  • This brand-new edition, now named Sherlock's Diseases of the Liver and Biliary System , after the late Professor Dame Sheila Sherlock, continues to provide concise clinical guidance for all those treating patients with hepato-biliary disease. (wiley.com)
  • We now have the tools to understand how RNA structural organization impacts disease and pathogen biology, with the eventual goal being to leverage this understanding for new drugs and antimicrobials," added Dr Nagarajan, the paper's co-lead author and Principal Investigator of Computational & Systems Biology at the GIS. (medindia.net)
  • Drug-induced liver injury is a cause of acute and chronic liver disease. (wikipedia.org)
  • Hoofnagle leads the Liver Disease Branch at NIDDK, and has done so since he was tapped for the position in 2003. (wikipedia.org)
  • American Association for the Study of Liver diseases distinguished achievement award 2001 Gold Medal from the Canadian Association for the Study of the Liver 2001, for contributions to liver disease research. (wikipedia.org)
  • 1991. Liver biopsy, interpretation for the 1990s: clinicopathologic correlations in liver disease (Chicago, III. (wikipedia.org)
  • NIH, Jay H. Hoofnagle, M.D., http://www.niddk.nih.gov/about-niddk/staff-directory/extramural/jay-hoofnagle/pages/biography.aspx NIH, New NIDDK Branch Focuses on Liver Disease, Jul. (wikipedia.org)
  • CDI cells enable new strategies for disease modeling and drug discovery work. (wikipedia.org)
  • CDI is actively engaged in a number of large-scale iPS cell reprogramming and banking projects, with the goal of creating broadly available resources of iPS cells that represent normal human diversity, disease states and adverse drug reactions. (wikipedia.org)

risk of liver

  • 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)
  • The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote, etc. (wikipedia.org)

inhibition

  • 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)

failure

  • 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. (massgeneral.org)
  • Whilst liver failure from bentazepam is considered to be rare, liver function monitoring has been recommended for all patients taking bentazepam. (wikipedia.org)
  • Over time the chronic form may progress to scarring of the liver, liver failure, or liver cancer. (wikipedia.org)
  • Further, Ketek seemed to cause liver problems, including "liver failure", to a greater extent than would be expected of a common-use antibiotic. (wikipedia.org)
  • Between the start of telithromycin's marketing in mid-2004 and September 2006, there were 13 cases of liver failure, including at least four deaths, vision problems, blackouts, syncope, and potentially fatal cases of myasthenia gravis. (wikipedia.org)

adverse

  • Danan G, Benichou C (1999) Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. (springer.com)

Mechanisms

  • Mechanisms of drug-induced liver injury: from bedside to bench. (wikipedia.org)
  • Several published studies have used CDI products to investigate mechanisms of toxicity and have leveraged cellular models to identify toxicity earlier in the drug development process. (wikipedia.org)

Hy's

  • Hy's 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. (wikipedia.org)

chemically

  • While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis. (wikipedia.org)

Diseases

  • It includes traumatic brain injury and insults to the brain resulting from strokes, tumors, or neurological diseases such as multiple sclerosis. (thefreedictionary.com)
  • Over the past 56 years, thousands of physicians have depended on Diseases of the Liver and Biliary System . (wiley.com)
  • Hoofnagle is the author of over 400 peer reviewed articles on liver diseases, and his Scopus h-index as of January 2014 is 69. (wikipedia.org)
  • American Association for the Study of Liver Diseases. (wikipedia.org)

acute liver

  • In the case of overdoses, the storage of GSH will not be enough for NAPQI detoxication, thereby resulting in acute liver injury. (wikipedia.org)
  • Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures. (wikipedia.org)

disorders

  • Benichou C (1990) Criteria of drug-induced liver disorders. (springer.com)
  • increased risks of suicide increased risks of hyponatremia and SIADH risk of seizures, if the person stops taking the drug abruptly risks to the fetus in women who are pregnant, specifically congenital malformations like spina bifida, and developmental disorders. (wikipedia.org)

investigational new

  • 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. (c-path.org)
  • CDI's products are used in high throughput screens, and have been used as supporting data in Investigational New Drug (IND) submissions to the FDA. (wikipedia.org)

interactions

  • 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)
  • 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)

metabolism

  • Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. (diva-portal.org)
  • Phase I of drug metabolism are bioactivation pathways, which are catalyzed by CYP450 enzymes, produce toxic metabolites and thus have the potential to damage cells. (wikipedia.org)
  • The unusual level of activity CYP450 enzymes might lead to the changes in drug metabolism and convert drugs into their more toxic forms. (wikipedia.org)
  • Drugs that decrease the metabolism of carbamazepine or otherwise increase its levels include erythromycin, cimetidine, propoxyphene, and calcium channel blockers. (wikipedia.org)

APAP

  • Similarly, when used as a solvent for APAP, DMSO again increased NKT cell numbers and induced IFN-γ and granzyme B expression in both cell types. (wiley.com)

transplant

  • In Zimmerman's analysis of 116 patients with hepatocellular injury and jaundice due to drug exposure, 76% went on to either require a liver transplant or died. (wikipedia.org)
  • A liver transplant may also be an option in certain cases. (wikipedia.org)
  • In January 2006, an article in the March issue of Annals of Internal Medicine was published, citing three recent drug-induced liver injury cases likely due to telithromycin, one resulting in a liver transplant and one in death. (wikipedia.org)

cause liver

  • Chemicals that cause liver injury are called hepatotoxins. (wikipedia.org)

enzyme

  • Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. (wiley.com)
  • Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests. (wikipedia.org)

inflammatory

  • Damage may be due to the initial injury and to any inflammatory response or swelling that occurs in the next 48 to 72 hr. (thefreedictionary.com)

Clinical

  • 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)
  • Liver toxicity limits the development of many therapeutic compounds and presents major challenges to both clinical medicine and to the pharmaceutical industry. (massgeneral.org)
  • Unexpected toxicity is one of the leading reasons that drugs are pulled from the market or from late stage clinical trials and toxicity issues greatly increase the cost of drug development. (wikipedia.org)

potentially

  • 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)

immune

  • 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)

patients

  • Spontaneous resolution occurs in most patients but return to normal liver function may take months. (springer.com)
  • 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)

hepatocellular

  • The pattern of injury was hepatocellular in all. (springer.com)

dietary supplements

  • Data produced from this network showed that dietary supplements account for nearly 20 percent of drug-induced liver injuries. (wikipedia.org)

Prognosis

  • The dose toxic to the liver is quite variable from person to person and is often thought to be lower in chronic alcoholics Measurement of blood level is important in assessing prognosis, higher levels predicting a worse prognosis. (wikipedia.org)

toxicities

  • Developing, approving and prescribing a drug requires that the therapeutic benefits be weighed against any potential toxicities. (massgeneral.org)
  • Type A drug reaction accounts for 80% of all toxicities. (wikipedia.org)

membrane vesicles

  • The inhibitory effect of 88 drugs (100 μM) on MRP3- and MRP4-mediated substrate transport was measured in membrane vesicles. (sigmaaldrich.com)

toxic

  • Toxication or toxification is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. (wikipedia.org)
  • Administration of Acetylcysteine, a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. (wikipedia.org)

Patient

  • they tend to overstate how long a patient might live. (wikipedia.org)

systemic

  • and initiation of a systemic hypersensitivity response (i.e., drug allergy) that damages the liver. (uspharmacist.com)

enzymes

  • Different classes of enzymes, such as P450-monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver. (wikipedia.org)
  • Grapefruit juice raises the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in the gut wall and in the liver. (wikipedia.org)

Observations

  • The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury. (wikipedia.org)

biological

  • Although DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. (wiley.com)

occurs

  • An injury that occurs when the head, cervical spine, or other body part is hit by a rapidly moving object. (thefreedictionary.com)
  • 1 If a dermatologic reaction occurs, discontinue eslicarbazepine acetate unless reaction is clearly not drug related. (drugs.com)

reactions

  • Non-living elements affect the abiotic chemical reactions. (wikipedia.org)