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    6739 results match your criteria Drug-Induced Hepatotoxicity

    1 OF 135

    Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats.
    Pharm Biol 2017 Dec;55(1):1809-1816
    a Department of Biology , School of Basic Sciences, Bu-Ali Sina University , Hamedan , Iran.
    Context: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects.

    Objective: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. Read More

    Death and Liver Transplantation within Two Years of Onset of Drug-Induced Liver Injury.
    Hepatology 2017 May 23. Epub 2017 May 23.
    Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
    Drug-induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities ispoorly characterized particularly when fatalities occur > 26 weeks after DILI onset. We analyzed patients in the U. Read More

    Good for the lung but bad for the liver? Garlic-induced hepatotoxicity following liver transplantation.
    J Clin Pharm Ther 2017 May 25. Epub 2017 May 25.
    Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA.
    What Is Known And Objective: Limited data exist surrounding the metabolism and safety of garlic supplements.

    Case Description: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio(®) (Allium sativum) for HPS and soon after had elevated liver function tests. Read More

    Evaluation of HepaRG cells for the assessment of indirect drug-induced hepatotoxicity using INH as a model substance.
    Hum Cell 2017 May 19. Epub 2017 May 19.
    Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany.
    HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Read More

    In silico Prediction of Drug-induced Liver Injury Based on Adverse Drug Reaction Reports.
    Toxicol Sci 2017 May 17. Epub 2017 May 17.
    Science and Information College, Qingdao Agricultural University, Qingdao 266109, China.
    Drug-induced liver injury (DILI) is a major cause of drug attrition. Currently existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for DILI. Furthermore, their practical applications were limited by lack of new hepatotoxicity data. Read More

    A lipidomic cell-based assay for studying drug-induced phospholipidosis and steatosis.
    Electrophoresis 2017 May 17. Epub 2017 May 17.
    Biomarkers and Precision Medicine Unit, Unidad Analítica, Instituto de Investigación Sanitaria, Fundación Hospital La Fe, Spain.
    Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Read More

    Drug-induced Liver Injury: The Hepatic Pathologist's Approach.
    Gastroenterol Clin North Am 2017 Jun;46(2):273-296
    Laboratory of Pathology, National Cancer Institute, 10 Center Drive, Building 10, Room 2S235, MSC 1500, Bethesda, MD 20892, USA. Electronic address:
    The evaluation of liver biopsies in suspected drug-induced liver injury (DILI) can be complex. The biopsy may be approached systematically, by identification of histologic lesions and then identification of the overall pattern of injury. Potential DILI must be separated from concomitant non-DILI liver disease. Read More

    A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy metabolism.
    J Toxicol Sci 2017 ;42(3):349-358
    Laboratory for Safety Assessment and ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corp.
    Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. Read More

    Troglitazone inhibits bile acid amidation: a possible risk factor for liver injury.
    Toxicol Sci 2017 May 9. Epub 2017 May 9.
    Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan.
    Troglitazone and pioglitazone were developed as thiazolidinedione-type anti-diabetes drugs, but only troglitazone was withdrawn from the markets due to severe liver injury. As both troglitazone and its sulfate metabolite are strong inhibitors of the bile salt export pump (BSEP), troglitazone-induced bile acid (BA) retention is thought to be one of the underlying mechanisms of liver injury. However, pioglitazone is also a strong BSEP inhibitor, indicating other mechanisms may also be involved in troglitazone-induced BA retention. Read More

    Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis.
    Int J Mol Sci 2017 May 9;18(5). Epub 2017 May 9.
    Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
    Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Read More

    Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.
    Clin Radiol 2017 May 2. Epub 2017 May 2.
    Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
    The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. Read More

    Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity.
    Indian J Med Res 2016 Dec;144(6):924-928
    Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
    Background & Objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH).

    Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Read More

    Hepatotoxicity of Antimycotics Used for Invasive Fungal Infections: In Vitro Results.
    Biomed Res Int 2017 4;2017:9658018. Epub 2017 Apr 4.
    Fraunhofer Institute for Cell Therapy and Immunology, EXIM, Rostock, Germany.
    Purpose. Drug-induced liver injury (DILI) is the most common cause of liver injury and a serious clinical problem; antimycotics are involved in approximately 3% of all DILI cases. The hepatotoxicity of many drugs, including the antimycotics, is poorly screened in human models. Read More

    Risk of Acute Liver Injury With Antiretroviral Therapy by Viral Hepatitis Status.
    Open Forum Infect Dis 2017 28;4(2):ofx012. Epub 2017 Jan 28.
    Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
    Background: The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status.

    Methods: We followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Read More

    Use of Primary Rat Hepatocytes for Prediction of Drug-Induced Mitochondrial Dysfunction.
    Curr Protoc Toxicol 2017 May 2;72:14.16.1-14.16.10. Epub 2017 May 2.
    Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
    Mitochondrial dysfunction plays a central role in drug-induced liver injury. To evaluate drug-induced mitochondrial impairment, several isolated mitochondria- or cell line-based assays have been reported. Among them, culturing HepG2 cells in galactose provides a remarkable method to assess mitochondrial toxicity by activating mitochondrial aerobic respiration. Read More

    A Multi-Parametric Fluorescent Assay for the Screening and Mechanistic Study of Drug-Induced Steatosis in Liver Cells in Culture.
    Curr Protoc Toxicol 2017 May 2;72:14.15.1-14.15.11. Epub 2017 May 2.
    Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe (IIS-La Fe), Valencia, Spain.
    Human hepatic cells have been used for drug safety risk evaluations throughout early development phases. They provide rapid, cost-effective early feedback to identify drug candidates with potential hepatotoxicity. This unit presents a cell-based assay to evaluate the risk of liver damage associated with steatogenic drugs. Read More

    CXCL16 deficiency attenuates acetaminophen-induced hepatotoxicity through decreasing hepatic oxidative stress and inflammation in mice.
    Acta Biochim Biophys Sin (Shanghai) 2017 Apr 28:1-9. Epub 2017 Apr 28.
    Department of Bioengineering, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
    Chemokine C-X-C ligand 16 (CXCL16), a single-pass Type I membrane protein belonging to the CXC chemokine family, is related to the inflammatory response in liver injury. In present study, we investigated the pathophysiological role of CXCL16, a unique membrane-bound chemokine, in acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were injected with APAP, and blood and tissue samples were harvested at different time points. Read More

    Donor-Dependent and Other Nondefined Factors Have Greater Influence on the Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell Derived Hepatocyte-Like Cells.
    Stem Cells Transl Med 2017 May;6(5):1321-1331
    MRC Centre for Drug Safety Science, Division of Molecular & Clinical Pharmacology, the Institute of Translational Medicine, the University of Liverpool, Liverpool, L69 3GE, United Kingdom.
    Drug-induced liver injury is the greatest cause of post-marketing drug withdrawal; therefore, substantial resources are directed toward triaging potentially dangerous new compounds at all stages of drug development. One of the major factors preventing effective screening of new compounds is the lack of a predictive in vitro model of hepatotoxicity. Primary human hepatocytes offer a metabolically relevant model for which the molecular initiating events of hepatotoxicity can be examined; however, these cells vary greatly between donors and dedifferentiate rapidly in culture. Read More

    Georgian Med News 2017 Feb(263):99-105
    Tbilisi State Medical University, Department of Pharmacotherapy; JSC "Curatio", Tbilisi, Georgia.
    Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. Read More

    A computational toxicogenomics approach identifies a list of highly hepatotoxic compounds from a large microarray database.
    PLoS One 2017 27;12(4):e0176284. Epub 2017 Apr 27.
    Computational Genomics Lab., Instituto Nacional de Medicina Genómica, Mexico City, México.
    The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Read More

    Drug-induced liver injury: Do we know everything?
    World J Hepatol 2017 Apr;9(10):491-502
    Tamara Alempijevic, Simon Zec, Tomica Milosavljevic, University of Belgrade, School of Medicine, 11000 Belgrade, Serbia.
    Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. Read More

    Metabolomic approaches in the discovery of potential urinary biomarkers of drug-induced liver injury (DILI).
    Crit Rev Toxicol 2017 Apr 24:1-17. Epub 2017 Apr 24.
    a UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy , University of Porto , Porto , Portugal.
    Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Read More

    Solithromycin: A novel ketolide antibiotic.
    Am J Health Syst Pharm 2017 Apr 21. Epub 2017 Apr 21.
    Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX
    Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed.

    Summary: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance. Read More

    Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice.
    J Agric Food Chem 2017 May 25;65(18):3684-3692. Epub 2017 Apr 25.
    College of Chinese Medicinal Materials, Jilin Agricultural University , Changchun 130118, China.
    Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Read More

    ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish.
    Int J Mol Sci 2017 Apr 19;18(4). Epub 2017 Apr 19.
    ZeClinics SL, PRBB (Barcelona Biomedical Research Park), 08003 Barcelona, Spain.
    Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. Read More

    Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.
    Clin Toxicol (Phila) 2017 Jun 15;55(5):346-351. Epub 2017 Feb 15.
    b School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences , Monash University , Clayton , Australia.
    Context: The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses.

    Objective: The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. Read More

    Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human-Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans.
    Int J Mol Sci 2017 Apr 12;18(4). Epub 2017 Apr 12.
    Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC., 23 Naganuki Hadano, Kanagawa 257-0024, Japan.
    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in vitro exploratory studies for this purpose. Read More

    Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri.
    Environ Toxicol Pharmacol 2017 Apr 4;52:129-137. Epub 2017 Apr 4.
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. Electronic address:
    Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. Read More

    Association of CYP2B6 gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a Chinese population.
    Infect Genet Evol 2017 Jul 5;51:198-202. Epub 2017 Apr 5.
    Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:
    Objectives: Antituberculosis drug-induced hepatotoxicity (ATDH) remains a common and severe challenge in tuberculosis (TB) chemotherapy. A growing number of studies have revealed that genetic polymorphisms affect an individual's susceptibility to ATDH. The aim of this study was to explore the role of cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene polymorphisms in the development of ATDH in Chinese TB patients. Read More

    Clinical and histologic features of Azathioprine-induced hepatotoxicity.
    Scand J Gastroenterol 2017 Apr 7:1-5. Epub 2017 Apr 7.
    c Department of Pathology, Faculty of Medicine , Thammasat University , Pathumthani , Thailand.
    Background: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity.

    Methods: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Read More

    Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs.
    OMICS 2017 Apr;21(4):207-216
    7 Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68 , KarolinskaInstitutet, Stockholm, Sweden .
    Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients. Read More

    Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats.
    Molecules 2017 Apr 7;22(4). Epub 2017 Apr 7.
    State Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
    The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Read More

    Comparative Modulation of Levels of Oxidative Stress in the Liver of Anti-tuberculosis Drug Treated Wistar Rats by Vitamin B12, Beta-carotene and Spirulina fusiformis: Role of NF-kB, iNOS, IL-6 and IL-10.
    J Cell Biochem 2017 Apr 7. Epub 2017 Apr 7.
    School of Bio Science and Technology, VIT University, Vellore.
    Purpose: Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH & RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. Read More

    The transformation in biomarker detection and management of drug-induced liver injury.
    Liver Int 2017 Apr 7. Epub 2017 Apr 7.
    Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC, USA.
    Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Read More

    Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes.
    Cell Biol Toxicol 2017 Apr 5. Epub 2017 Apr 5.
    Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
    Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. Read More

    Exploring Chronic Drug Effects on Microengineered Human Liver Cultures Using Global Gene Expression Profiling.
    Toxicol Sci 2017 Jun;157(2):387-398
    School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523.
    Global gene expression profiling is useful for elucidating a drug's mechanism of action on the liver; however, such profiling in rats is not very sensitive for predicting human drug-induced liver injury, while dedifferentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned cocultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the mechanism of action prior to the onset of overt hepatotoxicity. Read More

    Ciprofloxacin-induced Hepatotoxicity in a Healthy Young Adult.
    Cureus 2017 Feb 8;9(2):e1016. Epub 2017 Feb 8.
    Internal Medicine, Seton Hall University-St. Francis Medical Center, Trenton, NJ.
    Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that is widely used in the treatment of many common infections, including urinary tract infections (UTIs). Despite the increase in Escherichia coli resistance to ciprofloxacin, especially in the United States (US), clinicians continue to utilize the high bioavailability of this drug in urine to counter UTIs. A rare adverse effect following use of ciprofloxacin is drug-induced hepatitis. Read More

    An Automated Multiplexed Hepatotoxicity and CYP Induction Assay Using HepaRG Cells in 2D and 3D.
    SLAS Discov 2017 Jun 27;22(5):614-625. Epub 2017 Mar 27.
    1 Likarda, LLC, Kansas City, KS, USA.
    Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e. Read More

    Drug-induced liver injury: recent advances in diagnosis and risk assessment.
    Gut 2017 Jun 23;66(6):1154-1164. Epub 2017 Mar 23.
    National Institute for Health Research (NIHR), Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
    Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. Read More

    Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB centre in the UK.
    BMC Infect Dis 2017 Mar 24;17(1):231. Epub 2017 Mar 24.
    Department of Infection, Northwick Park Hospital, London North West Healthcare NHS Trust, London, UK.
    Background: We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI.

    Methods: We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded. Read More

    Prevalence of hepatitis C virus and human immunodeficiency virus in a group of patients newly diagnosed with active tuberculosis in Porto Alegre, Southern Brazil.
    Mem Inst Oswaldo Cruz 2017 Apr;112(4):255-259
    Secretaria Estadual da Saúde do Rio Grande do Sul, Fundação Estadual de Produção e Pesquisa em Saúde, Centro de Desenvolvimento Científico e Tecnológico, Porto Alegre, RS, Brasil.
    Background: Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy.

    Objectives: The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status. Read More

    Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor.
    J Hepatol 2017 Mar 18. Epub 2017 Mar 18.
    University of Michigan, Ann Arbor, MI, USA. Electronic address:
    Background & Aims: Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline drug-induced liver injury (DILI) in a well-phenotyped cohort of patients.

    Methods: Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Read More

    Comparative pharmacokinetic evaluation of lopinavir and lopinavir-loaded solid lipid nanoparticles in hepatic impaired rat model.
    J Pharm Pharmacol 2017 Mar 19. Epub 2017 Mar 19.
    Novartis Healthcare, Hyderabad, Telangana, India.
    Objective: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. Read More

    Drug Rechallenge Following Drug-Induced Liver Injury.
    Hepatology 2017 Mar 13. Epub 2017 Mar 13.
    Global Patient Safety, Eli Lilly and Company, Indianapolis, IN.
    Drug induced hepatocellular injury is identified internationally by ALT 5x upper limits normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decreases by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT 3-5xULN or greater. Read More

    First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors.
    Pan Afr Med J 2016 16;25:167. Epub 2016 Nov 16.
    Faculté des Sciences, Universités Ibn Tofail, Kénitra, Maroc.
    In our days, tuberculosis, whet ever its localization, became a curable disease. The cornerstone is a 6 month course of isoniazid, rifampicine and pyrazinamide. All of the three first line antituberculosis drugs may induce hepatic damage which may have negative consequences for treatment outcome. Read More

    HLA-B(*)57 Allele Is Associated with Concomitant Anti-tuberculosis and Antiretroviral Drugs Induced Liver Toxicity in Ethiopians.
    Front Pharmacol 2017 27;8:90. Epub 2017 Feb 27.
    Department of Laboratory Medicine, Karolinska Institutet-Karolinska University Hospital Stockholm, Sweden.
    Drug-induced liver injury (DILI) is a known adverse effect of both anti-tuberculosis (anti-TB) and antiretroviral (ARV) drugs. Recent studies highlight the implications of genetic predispositions to DILI. We performed a case-control study to identify Human Leukocyte Antigen-B (HLA-B) variant alleles associated with anti-TB and ARV co-treatment induced liver toxicity in Ethiopian TB and HIV co-infected patients. Read More

    Drug-induced liver injury due to antibiotics.
    Scand J Gastroenterol 2017 Jun - Jul;52(6-7):617-623. Epub 2017 Feb 20.
    a The National University Hospital of Iceland and Faculty of Medicine , Reykjavik , Iceland.
    Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. Read More

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