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https://www.readbyqxmd.com/read/28108666/antibiotic-induced-elevations-of-plasma-bile-acids-in-rats-independent-of-bsep-inhibition
#1
Yutai Li, Michael J Hafey, Hong Duong, Raymond Evers, Kyeongmi Cheon, Daniel J Holder, Alema Galijatovic-Idrizbegovic, Frank D Sistare, Warren E Glaab
Drug-induced liver injury (DILI) is a common toxicity observed in drug development and can lead to withdrawal of approved drugs from the market. To better understand the numerous mechanisms of DILI, recent efforts have focused on transporter inhibition, specifically liver canalicular bile salt export pump (Bsep) as one mechanism of DILI, and on the potential use of plasma bile acids as monitorable mechanism-based biomarkers of Bsep inhibition. To explore alternative mechanisms of bile acid increases in plasma, six antibiotic and two non-antibiotic drugs unlikely to be Bsep inhibitors were evaluated in rat studies...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28105256/drug-induced-liver-injury-towards-early-prediction-and-risk-stratification
#2
REVIEW
Emanuel Raschi, Fabrizio De Ponti
Drug-induced liver injury (DILI) is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications and agents listed as causing liver damage (http://livertox.nih.gov/). As it was the case in the past decade with drug-induced QT prolongation/arrhythmia, there is an urgent unmet clinical need to develop tools for risk assessment and stratification in clinical practice and, in parallel, to improve prediction of pre-clinical models to support regulatory steps and facilitate early detection of liver-specific adverse drug events...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28092392/the-in-silico-identification-of-human-bile-salt-export-pump-abcb11-inhibitors-associated-with-cholestatic-drug-induced-liver-injury
#3
Lili Xi, Jia Yao, Yuhui Wei, Xin'an Wu, Xiaojun Yao, Huanxiang Liu, Shuyan Li
Drug-induced liver injury (DILI) is one of the major causes of drug attrition and failure. Currently, there is increasing evidence that direct inhibition of the human bile salt export pump (BSEP/ABCB11) by drugs and/or metabolites is one of the most important mechanisms of cholestatic DILI. In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28091407/clinical-characteristics-of-patients-with-drug-induced-liver-injury
#4
Li-Xia Yang, Cheng-Yuan Liu, Lun-Li Zhang, Ling-Ling Lai, Ming Fang, Chong Zhang
BACKGROUND: Drug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28074540/complications-of-percutaneous-liver-biopsy-with-klatskin-needles-a-36-year-single-centre-experience
#5
V Takyar, O Etzion, T Heller, D E Kleiner, Y Rotman, M G Ghany, N Fryzek, V H Williams, E Rivera, S Auh, T J Liang, J H Hoofnagle, C Koh
BACKGROUND: Liver biopsy is the gold standard in evaluating liver diseases but is susceptible to complications. Safety data on aspiration needle biopsies remain limited. AIM: To evaluate the safety of percutaneous liver biopsy performed with Klatskin needle. METHODS: Clinical and biochemical data were retrospectively retrieved from sequential subjects who underwent liver biopsy with Klatskin needle from 1978 to 2015. Subjects with complications underwent thorough chart reviews for hospital course...
January 10, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28069987/transgenic-zebrafish-reporter-lines-as-alternative-in-vivo-organ-toxicity-models
#6
Kar Lai Poon, Xingang Wang, Serene Gp Lee, Ashley S Ng, Wei Huang Goh, Zhonghua Zhao, Muthafar Al-Haddawi, Haishan Wang, Sinnakaruppan Mathavan, Phillip W Ingham, Claudia Mcginnis, Tom J Carney
Organ toxicity, particularly liver toxicity, remains one of the major reasons for termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would therefore find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28063906/pyrazinamide-induced-hepatotoxicity-is-alleviated-by-4-pba-via-inhibition-of-the-perk-eif2%C3%AE-atf4-chop-pathway
#7
Hong-Li Guo, Hozeifa M Hassan, Ping-Ping Ding, Shao-Jie Wang, Xi Chen, Tao Wang, Li-Xin Sun, Lu-Yong Zhang, Zhen-Zhou Jiang
Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. In this study, we describe the role of ER stress in PZA induced hepatotoxicity in vivo and in vitro. We found that PZA induces apoptosis in HepG2 cells, and causes liver damage in rats, characterized by increased serum ALT, AST and TBA levels...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28054388/good-outcome-of-living-donor-liver-transplantation-in-drug-induced-acute-liver-failure-a-single-centre-experience
#8
Narendra Singh Choudhary, Sanjiv Saigal, Neeraj Saraf, Amit Rastogi, Sanjay Goja, Prashant Bhangui, Vijay Vohra, Deepak Govil, Arvinder S Soin
INTRODUCTION: Drug induced acute liver failure (ALF) is associated with high mortality. There is limited literature on results of living donor liver transplantation (LDLT). MATERIAL AND METHODS: The study was conducted at a tertiary care centre in North India. All patients who received LDLT for drug induced ALF were included. The data is shown as median (IQR). RESULTS: A total of 18 patients (15 females and 3 males), aged 34(25-45) years, underwent LDLT for DILI related ALF...
January 5, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28053072/the-promise-of-new-technologies-to-reduce-refine-or-replace-animal-use-while-reducing-risks-of-drug-induced-liver-injury-in-pharmaceutical-development
#9
Frank D Sistare, William B Mattes, Edward L LeCluyse
Drug induced liver injury (DILI) has contributed more to marketed pharmaceutical withdrawals and clinical development failures than any other human organ toxicity. DILI seen in animal studies also frequently leads to the discontinuation of promising drug candidates very early in the pipeline. This manuscript reviews and critically assesses the current regulatory expectations; the current drug development approaches, strategies, and gaps; and the numerous exciting opportunities becoming available to address these gaps through technological advances...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28049998/drug-induced-liver-injury-associated-with-mosapride-citrate-a-report-of-two-cases
#10
Ayaka Sako, Sung Kwan Bae, Toshifumi Gushima, Junichi Motoshita, Shigemune Bekki, Seigo Abiru, Atsumasa Komori, Shinji Shimoda, Masahiro Ito, Hiroshi Yatsuhashi, Kazuhiro Takahashi
We herein report two cases of drug-induced liver injury (DILI) due to mosapride. Case 1: A 78-year-old man was admitted with elevated transaminase levels. The cessation of mosapride led to the improvement of elevated liver enzyme levels. Case 2: A 54-year-old man was admitted with jaundice. Mosapride was discontinued immediately, and methylprednisolone was administered for acute liver failure. The patient's data showed improvement, and he was discharged on Day 32. In both cases, mosapride gave a positive response to a drug-induced lymphocyte stimulation test (DLST), and the patient's score based on the criteria for DILI was "highly probable"...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28043905/association-of-liver-injury-from-specific-drugs-or-groups-of-drugs-with-polymorphisms-in-hla-and-other-genes-in-a-genome-wide-association-study
#11
Paola Nicoletti, Guruprasad P Aithal, Einar S Bjornsson, Raul J Andrade, Ashley Sawle, Marco Arrese, Huiman X Barnhart, Emmanuelle Bondon-Guitton, Paul H Hayashi, Fernando Bessone, Alfonso Carvajal, Ingolf Cascorbi, Elizabeth T Cirulli, Naga Chalasani, Anita Conforti, Sally A Coulthard, Mark J Daly, Christopher P Day, John F Dillon, Robert J Fontana, Jane I Grove, Pär Hallberg, Nelia Hernández, Luisa Ibáñez, Gerd A Kullak-Ublick, Tarja Laitinen, Dominique Larrey, M Isabel Lucena, Anke H Maitland-van der Zee, Jennifer H Martin, Mariam Molokhia, Munir Pirmohamed, Elizabeth E Powell, Shengying Qin, Jose Serrano, Camilla Stephens, Andrew Stolz, Mia Wadelius, Paul B Watkins, Aris Floratos, Yufeng Shen, Matthew R Nelson, Thomas J Urban, Ann K Daly
BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10588 population-matched controls. The first set of cases was recruited prior to May 2009 in Europe (n=137) or the USA (n=274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the USA and South America...
December 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/28028769/are-polymorphisms-in-genes-relevant-to-drug-disposition-predictors-of-susceptibility-to-drug-induced-liver-injury
#12
Ann K Daly
Despite considerable progress in identifying specific HLA alleles as genetic risk factors for some forms of drug-induced liver injury, progress in understanding whether genetic polymorphisms relevant to drug disposition also contribute to risk for developing this serious toxicity has been more limited. Evidence from both candidate-gene case control studies and genome-wide association studies is now discussed. In the case of genes relevant to drug metabolism, polymorphisms in cytochromes P450, UDP-glucuronosyltransferases, N-acetyltransferases and glutathione S-transferases as risk factors for DILI are assessed...
December 27, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/28028586/role-of-mirna-and-its-potential-as-a-novel-diagnostic-biomarker-in-drug-induced-liver-injury
#13
REVIEW
Sukumaran Sanjay, Chandrashekaran Girish
PURPOSE: MicroRNAs (miRNA or miR) are the most abundant and stable class of small RNA. Unlike the typical RNA molecules present in the cell, they do not encode proteins but can control translation. and Hhence, they are found to play a major role in the regulation of cellular processes. miRNAs have been shown to differentially regulate various genes, and the expression levels of some miRNAs changes several fold in liver and serum, during drug- induced toxicity. This review summarises some of the latest findings about the biological functions of miRNA and its potential use as diagnostic biomarkers in drug- induced liver injury...
December 27, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28005582/analysis-of-immunogenetic-factors-in-idiosyncratic-drug-induced-liver-injury-in-the-paediatric-population
#14
Esther Ocete-Hita, Ma José Salmerón-Fernández, Emilia Urrutia-Maldonado, Paloma Muñoz de Rueda, María Salmerón-Ruiz, Ma Carmen Martinez-Padilla, Angela Ruiz-Extremera
OBJECTIVE: Idiosyncratic drug-induced liver injury (DILI) is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes which limit the extent of damage, can determine susceptibility and make individuals unique in their development of hepatotoxicity. The aim of this study is to analyse the genetic factors (HLA, cytokine polymorphisms and KIR genotype) of children who experience an episode of drug-induced liver injury...
December 22, 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/27978926/-current-status-of-chinese-herbal-preparations-included-in-livertox-database
#15
R Jin, H Y Gu, L L Li, L L Sun
Objective: To investigate the contents and features of drug-induced liver injury (DILI) database called LiverTox, as well as 37 herbal preparations included in this database. Methods: Firstly, the source and contents of LiverTox were briefly introduced, including the clinical features, types, severity, and causality assessment scale of DILI. Secondly, detailed information of 37 herbal preparations included in the class of "Herbals and Dietary Supplements" were extracted, including drug name, origin, efficacy, constituents, type of liver injury, and manifestations, to perform a preliminary statistical analysis...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27978925/-serological-and-pathological-features-of-drug-induced-liver-injury-and-autoimmune-hepatitis
#16
Z L Jiang, P Li, J L Wang, Q H Yang, Y G Liu, R F Shi, Y Q Mi
Objective: To investigate the differences and similarities between drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) in serum biochemical parameters and liver pathology, and to provide some thoughts for clinical diagnosis and differentiation of these two diseases. Methods: A retrospective analysis was performed for the biochemical, immunological, autoantibody, and liver pathological data of 106 DILI patients and 63 AIH patients who were hospitalized, diagnosed, and treated in our hospital from January 2012 to October 2014...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27978924/-promoting-translational-research-on-drug-induced-liver-injury
#17
Y M Mao
Drug-induced liver injury (DILI) is one of the most important drug-induced diseases and an important reason for failure to obtain approval, an increase in warnings, and withdrawal from market. DILI has a complex clinical phenotype and can cause almost all types of acute, subacute, and chronic liver injury, and it may cause liver failure and even death in patients with severe conditions. The diversity of drugs involved and heterogeneity of populations are the main reasons for unpredictability of most DILI cases in clinical practice...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27978923/-current-status-of-the-treatment-of-drug-induced-liver-injury
#18
H Zhao, W Xie
In recent years, with the amazing increase in the number of prescription drugs and non-prescription drugs and the irrational use of Chinese herbal medicine and healthcare products, the incidence of drug-induced liver injury (DILI) has been increasing year by year; however, there is still a lack of effective therapeutic methods for DILI at present. Standard treatment based on timely diagnosis should be emphasized, and it is necessary to fully evaluate the severity of liver injury and primary disease, withdraw suspected drugs in time, and select appropriate drugs...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27978922/-carefully-reviewing-the-history-of-diagnostic-scales-and-paying-more-attention-to-the-diagnostic-value-of-roussel-uclaf-causality-assessment-method-scale-for-drug-induced-liver-injury
#19
C W Chen
Currently, the diagnostic criteria for drug-induced liver injury (DILI) used in the clinical studies and related literature in China are very confusing, making it difficult to compare and extend the use of the results, conclusions, and experience of these studies. Therefore, it is necessary to carefully review the developmental history of diagnostic scales and unify the diagnostic criteria and related knowledge of DILI. Since its publication in 1993, Roussel Uclaf Causality Assessment Method (RUCAM) scale has been widely used to assess the causality between drugs and liver injury, both in DILI studies and decisions on the regulation of drugs which may cause liver injury, in order to provide a useful analytical framework for clinical physicians in the diagnosis of DILI...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27978773/a-longitudinal-assessment-of-mir-122-and-gldh-as-biomarkers-of-drug-induced-liver-injury-in-the-rat
#20
Petra Thulin, Robert J Hornby, Mariona Auli, Gunnar Nordahl, Daniel J Antoine, Philip Starkey Lewis, Christopher E Goldring, B Kevin Park, Neus Prats, Björn Glinghammar, Ina Schuppe-Koistinen
CONTEXT: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies. OBJECTIVE: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH)...
December 15, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
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