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drug-induced liver injury

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https://www.readbyqxmd.com/read/28543844/death-and-liver-transplantation-within-two-years-of-onset-of-drug-induced-liver-injury
#1
Paul H Hayashi, Don Rockey, Robert J Fontana, Hans L Tillmann, Neil Kaplowitz, Huiman Barnhart, Jiezhan Gu, Naga P Chalasani, K Rajender Reddy, Averell H Sherker, Jay H Hoofnagle
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.S. Drug-Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by 8 Network investigators and categorized as DILI having a primary, contributory or no role in the fatality...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543822/good-for-the-lung-but-bad-for-the-liver-garlic-induced-hepatotoxicity-following-liver-transplantation
#2
S A Shaikh, S Tischer, E K Choi, R J Fontana
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. Garlicin Cardio(®) was discontinued and liver enzymes normalized...
May 25, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28539989/hepatic-complications-induced-by-immunosuppressants-and-biologics-in-inflammatory-bowel-disease
#3
REVIEW
My-Linh Tran-Minh, Paula Sousa, Marianne Maillet, Matthieu Allez, Jean-Marc Gornet
The incidence of inflammatory bowel diseases (IBD) is rising worldwide. The therapeutic options for IBD are expanding, and the number of drugs with new targets will rapidly increase in coming years. A rapid step-up approach with close monitoring of intestinal inflammation is extensively used. The fear of side effects represents one the most limiting factor of their use. Despite a widespread use for years, drug induced liver injury (DILI) management remains a challenging situation with Azathioprine and Methotrexate...
May 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#4
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28536862/mechanisms-of-hepatotoxicity-associated-with-the-monocyclic-%C3%AE-lactam-antibiotic-bal30072
#5
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A Howell, Rachel J Church, Jeff Woodhead, Marc Engelhardt, Stephan Krähenbühl, Martina Maurer
BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. Despite the absence of liver toxicity in preclinical studies in rats and marmosets and in single dose clinical studies in humans, increased transaminase activities were observed in healthy subjects in multiple-dose clinical studies. We, therefore, initiated a comprehensive program to find out the mechanisms leading to hepatocellular injury using HepG2 cells (human hepatocellular carcinoma cell line), HepaRG cells (inducible hepatocytes derived from a human hepatic progenitor cell line), and human liver microtissue preparations...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#6
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#7
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days...
May 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#8
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28526132/old-and-novel-functions-of-caspase-2
#9
M A Miles, T Kitevska-Ilioski, C J Hawkins
Although caspase-2 is a highly conserved protease that has received a lot of research attention, consensus about its roles and the molecular mechanisms that underpin them has been elusive. Recent improvements to our understanding of the activities of caspase-2 have been facilitated by the development and refinement of techniques allowing identification of cellular processes instigated by this caspase. Following DNA damage, caspase-2 can be activated in a molecular complex called the "PIDDosome"; however, other stimuli provoke caspase-2-dependent activities that do not appear to involve this complex...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28525267/the-supernatant-from-hepatocyte-cultures-with-drugs-that-cause-idiosyncratic-liver-injury-activates-macrophage-inflammasomes
#10
Ryuji Kato, Jack Uetrecht
There is increasing evidence that most idiosyncratic drug-induced liver injury (IDILI) is immune mediated, and in most cases reactive metabolites appear to be responsible for induction of this immune response. Reactive metabolites can cause cell damage with the release of damage-associated molecular patterns (DAMPs), which is thought to be involved in immune activation. Presumably the reason that the liver is a common target of idiosyncratic drug reactions is because it is the major site of drug metabolism and reactive metabolite formation...
May 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28524372/herbal-formula-baogan-yihao-bgyh-prevented-dimethylnitrosamine-dmn-induced-liver-injury-in-rats
#11
Xiujie Liu, Jing Su, Yu Shi, Ying Guo, Imran Suheryani, Shicong Zhao, Yulin Deng, Weiwei Meng, Yan Chen, Lili Sun, Rongji Dai
Preclinical Research Baogan Yihao (BGYH) is a traditional Chinese herbal medicine for the treatment of chronic liver diseases. In this study, the effects of BGYH on dimethylnitrosamine (DMN)-induced liver fibrosis were investigated using a rat model. BGYH alleviate liver damage, as indicated by decreased levels of AST, ALT, γ-GT, and AKP. BGYH also prevented collagen deposition and reduced pathological tissue injury in liver tissue. In fibrosis, high levels of α-SMA and TGF-β in liver tissue were markedly attenuated by BGYH...
May 19, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#12
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28523534/idiosyncratic-drug-induced-liver-injury-linked-to-polygonum-multiflorum-a-case-study-by-pharmacognosy
#13
Chun-Yu Li, Qin He, Dan Gao, Rui-Yu Li, Yun Zhu, Hui-Fang Li, Wu-Wen Feng, Mei-Hua Yang, Xiao-He Xiao, Jia-Bo Wang
No abstract text is available yet for this article.
May 18, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28521054/in-silico-prediction-of-drug-induced-liver-injury-based-on-adverse-drug-reaction-reports
#14
Xiang-Wei Zhu, Shao-Jing Li
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. In this study, we first collected and curated a novel set of 122 DILI-positive and 932 DILI-negative drugs from online adverse drug reports using proportional reporting ratios as the signal detection method. Second, three strategies (under-sampling the majority class, synthetic minority over-sampling technique, and adjusting decision threshold approach) were employed to develop predictive classification models to cope with the unbalanced dataset...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28520417/correction-to-evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#15
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
No abstract text is available yet for this article.
May 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28508325/preliminary-results-of-a-novel-algorithmic-method-aiming-to-support-initial-causality-assessment-of-routine-pharmacovigilance-case-reports-for-medication-induced-liver-injury-the-pv-rucam
#16
Erik Scalfaro, Henk Johan Streefkerk, Michael Merz, Christoph Meier, David Lewis
INTRODUCTION: Data incompleteness in pharmacovigilance (PV) health records limits the use of current causality assessment methods for drug-induced liver injury (DILI). In addition to the inherent complexity of this adverse event, identifying cases of high causal probability is difficult. OBJECTIVE: The aim was to evaluate the performance of an improved, algorithmic and standardised method called the Pharmacovigilance-Roussel Uclaf Causality Assessment Method (PV-RUCAM), to support assessment of suspected DILI...
May 15, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28507720/in-vivo-imaging-of-leucine-aminopeptidase-activity-in-drug-induced-liver-injury-and-liver-cancer-via-a-near-infrared-fluorescent-probe
#17
Xinyuan He, Lihong Li, Yu Fang, Wen Shi, Xiaohua Li, Huimin Ma
The liver, a main detoxification organ, has evolved a complex enzymatic system to respond to multiple pathological conditions, in which leucine aminopeptidase (LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity in liver disease models is thus helpful to further understand the function of LAP in detoxification and medicine, but such an imaging approach is still lacking. Herein, we develop a selective and sensitive near-infrared fluorescent probe (HCAL) for this purpose...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28506899/hepatoprotective-activities-of-antrodia-camphorata-and-its-triterpenoid-compounds-against-ccl4-induced-liver-injury-in-mice
#18
Zi-Wei Li, Yi Kuang, Shu-Nan Tang, Kai Li, Yun Huang, Xue Qiao, Si-Wang Yu, Yew-Min Tzeng, Jen-Yu Lo, Min Ye
ETHNOPHARMACOLOGY RELEVANCE: Antrodia camphorata (AC) is a rare and precious fungus indigenous to Taiwan used as a traditional medicine for the treatment of liver injury. Triterpenoids are the major bioactive constituents of A. camphorata and have been reported to possess hepatoprotective activities. To meet the increasing demand, artificial cultivation techniques have been developed. AIM OF THE STUDY: This study aims to evaluate the hepatoprotective activities of AC samples derived from different cultivation techniques and to dissect the main active triterpenoid compounds...
May 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28506368/human-immunodeficiency-virus-infection-antiretroviral-therapy-and-liver-pathology
#19
REVIEW
Mark W Sonderup, Helen Cecilia Wainwright
The improvement in antiretroviral therapy has significantly impacted the lives of people living with human immunodeficiency virus (HIV). In high-income countries, HIV deaths are predominated by liver disease consequent to viral hepatitis coinfection, alcohol, and nonalcoholic fatty liver disease. Published liver pathology findings have shifted from being predominated by opportunistic infections to the metabolic effects of HIV and antiretroviral therapy as well as drug-induced liver injuries. Differences remain between high-income and low-income countries, where opportunistic infections and immune reconstitution syndromes, dominate findings...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28506365/drug-induced-liver-injury-the-hepatic-pathologist-s-approach
#20
REVIEW
David E Kleiner
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. The findings can be analyzed with respect to the various prescription and nonprescription medications and dietary supplements under suspicion to provide a complete interpretation of the findings. The pathologic findings, the histologic differential diagnosis, and expert interpretation are part of a complete biopsy assessment and provide information that is of greatest value in patient management...
June 2017: Gastroenterology Clinics of North America
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