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

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 ...

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 ...

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. ...

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.

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 ...

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 ...

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. ...

Description of disease Drug-induced hepatitis. Treatment Drug-induced hepatitis. Symptoms and causes Drug-induced hepatitis Prophylaxis Drug-induced hepatitis

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)

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

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 - ...

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 ...

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

EASL Clinical Practice Guideline presents the available evidence on risk factors, diagnosis, management, risk minimization for Drug-Induced Liver Injury.

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 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 ...

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 transparency using data provided through the Freedom of Information Act (FOIA)

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 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 ...

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 ...

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.

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European Union agency responsible for the protection of public and animal health through the scientific evaluation and supervision of medicines.

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 [46]. 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 ...

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 …

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].

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 ...

Weiwei Shan, Christopher J. Nicol, Shinji Ito, Moses T. Bility, Mary J. Kennett, Jerrold M. Ward, Frank J. Gonzalez, Jeffrey M. ...

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 ...

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

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 ...

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 ...

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

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.

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 ...

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.

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 ...

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, ...

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

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

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 ...

www.MOLUNA.de Operative Techniques for Severe Liver Injury [4214048] - 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

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 ...

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 ...

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. ...