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Drug induced liver injury

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https://www.readbyqxmd.com/read/28323125/minocycline-hepatotoxicity-clinical-characterization-and-identification-of-hla-b%C3%A2-35-02-as-a-risk-factor
#1
Thomas Jacob Urban, Paola Nicoletti, Naga Chalasani, Jose Serrano, Andrew Stolz, Ann Daly, Guruprasad Aithal, John Dillon, Victor Navarro, Joseph Odin, Huiman Barnhart, David Ostrov, Nanye Long, Elizabeth Theresa Cirulli, Paul Brent Watkins, Robert John Fontana
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 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. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28322066/hepatoprotective-effect-against-ccl4-induced-acute-liver-damage-in-mice-and-high-performance-liquid-chromatography-mass-spectrometric-method-for-analysis-of-the-constituents-of-extract-of-rubus-crataegifolius
#2
Yongjiao Sun, Lingyun Jia, Zhanbo Huang, Jing Wang, Jincai Lu, Jing Li
This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl4. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts...
March 21, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28321390/metabonomics-research-progress-on-liver-diseases
#3
REVIEW
Mengqian Yu, Ying Zhu, Qingwei Cong, Chunyan Wu
Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28320086/antifibrotic-effect-of-diethylcarbamazine-combined-with-hesperidin-against-ethanol-induced-liver-fibrosis-in-rats
#4
Alaa El-Din El-Sayed El-Sisi, Samia Salim Sokar, Abdelhadi Mohamed Shebl, Dina Zakaria Mohamed
Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100mg/kg)...
March 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28315126/screening-for-main-components-associated-with-the-idiosyncratic-hepatotoxicity-of-a-tonic-herb-polygonum-multiflorum
#5
Chunyu Li, Ming Niu, Zhaofang Bai, Congen Zhang, Yanling Zhao, Ruiyu Li, Can Tu, Huifang Li, Jing Jing, Yakun Meng, Zhijie Ma, Wuwen Feng, Jinfa Tang, Yun Zhu, Jinjie Li, Xiaoya Shang, Zhengsheng Zou, Xiaohe Xiao, Jiabo Wang
The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats...
March 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28304119/serum-markers-for-mitochondrial-dysfunction-and-cell-death-are-possible-predictive-indicators-for-drug-induced-liver-injury-by-direct-acting-antivirals
#6
Keisuke Kakisaka, Yuichi Yoshida, Yuji Suzuki, Takuro Sato, Hidekatsu Kuroda, Akio Miyasaka, Yasuhiro Takikawa
BACKGROUND & AIM: We prospectively screened patients treated with direct-acting antivirals (DAAs) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). METHODS: The levels of various serum markers among DILI, non-DILI, and control groups were compared. The DILI group consisted of 8 patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, gender, and disease severity...
March 17, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28303974/antifibrotic-effect-of-pirfenidone-in-a-mouse-model-of-human-nonalcoholic-steatohepatitis
#7
Chikara Komiya, Miyako Tanaka, Kyoichiro Tsuchiya, Noriko Shimazu, Kentaro Mori, Shunsaku Furuke, Yasutaka Miyachi, Kumiko Shiba, Shinobu Yamaguchi, Kenji Ikeda, Kozue Ochi, Kazuhiko Nakabayashi, Ken-Ichiro Hata, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis with lobular inflammation and hepatocyte injury. Pirfenidone (PFD) is an orally bioavailable pyridone derivative that has been clinically used for the treatment of idiopathic pulmonary fibrosis. However, it remains unknown whether PFD improves liver fibrosis in a mouse model with human NASH-like phenotypes. In this study, we employed melanocortin 4 receptor-deficient (MC4R-KO) mice as a mouse model with human NASH-like phenotypes to elucidate the effect and action mechanisms of PFD on the development of NASH...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295448/drug-rechallenge-following-drug-induced-liver-injury
#8
REVIEW
Christine M Hunt, Julie I Papay, Vid Stanulovic, Arie Regev
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. Nearly 50 drugs are associated with positive rechallenge after drug-induced liver injury (DILI): antimicrobials, central nervous system, cardiovascular and oncology therapeutics...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28294319/grpr-antagonist-protects-from-drug-induced-liver-injury-by-impairing-neutrophil-chemotaxis-and-motility
#9
Rafael S Czepielewski, Natália Jaeger, Pedro E Marques, Maísa M Antunes, Maurício M Rigo, Débora M Alvarenga, Rafaela V Pereira, Rodrigo D da Silva, Tiago G Lopes, Vinícius D da Silva, Bárbara N Porto, Gustavo B Menezes, Cristina Bonorino
Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXCR2 ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration and mechanisms underlying this phenomenon...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28293388/protective-role-of-licochalcone-b-against-ethanol-induced-hepatotoxicity-through-regulation-of-erk-signaling
#10
Xiao-Peng Gao, Dong-Wei Qian, Zhen Xie, Hao Hui
OBJECTIVES: Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study. MATERIALS AND METHODS: An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28292360/acute-on-chronic-liver-failure-causes-clinical-characteristics-and-predictors-of-mortality
#11
Abbas Ali Tasneem, Nasir Hassan Luck
OBJECTIVE: To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. METHODOLOGY: All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included...
January 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28289388/hla-b-57-allele-is-associated-with-concomitant-anti-tuberculosis-and-antiretroviral-drugs-induced-liver-toxicity-in-ethiopians
#12
Zelalem Petros, Junko Kishikawa, Eyasu Makonnen, Getnet Yimer, Abiy Habtewold, Eleni Aklillu
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. A total of 495 newly diagnosed TB and HIV co-infected patients were enrolled and received rifampicin based anti-TB and efavirenz based ARV therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#13
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28281441/miliary-tuberculosis
#14
Surendra K Sharma, Alladi Mohan
Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28279082/effects-of-immunization-and-checkpoint-inhibition-on-amodiaquine-induced-liver-injury
#15
Alastair Mak, Alexander Johnston, Jack Uetrecht
If idiosyncratic drug-induced liver injury (IDILI) is immune-mediated, it is possible that an individual's prior exposure to antigens may affect their susceptibility to IDILI. An individual's repertoire of memory immune cells is shaped by every past exposure to antigens. Subsequent drug-induced adverse drug reactions may therefore involve an immune cell's cross reactivity between a prior antigen and resulting drug-modified proteins. Therefore in this experiment, mice were immunized with amodiaquine (AQ)-modified hepatic proteins to mimic a previous exposure; treated with a RIBI adjuvant and anti-CD40 antibodies to stimulate an immune response; and, treated with anti-PD1 and anti-CTLA-4 antibodies prior to AQ treatment in order to overcome immune tolerance...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28277649/development-of-liver-decellularized-extracellular-matrix-bioink-for-3d-cell-printing-based-liver-tissue-engineering
#16
Hyungseok Lee, Wonil Han, Hyeonji Kim, Dong-Heon Ha, Jinah Jang, Byoung Soo Kim, Dong-Woo Cho
The liver is an important organ and plays major roles in the human body. Due to the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation...
March 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28276834/drug-induced-liver-injury-due-to-antibiotics
#17
Einar S Björnsson
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. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion...
February 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28271527/the-role-of-lncrna-h19-in-gender-disparity-of-cholestatic-liver-injury-in-mdr2-mice
#18
Xiaojiaoyang Li, Runping Liu, Jing Yang, Lixin Sun, Luyong Zhang, Zhenzhou Jiang, Puneet Puri, Emily C Gurley, Guanhua Lai, Yuping Tang, Zhiming Huang, William M Pandak, Phillip B Hylemon, Huiping Zhou
The multi-drug resistance 2 knockout (Mdr2(-/-) ) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2(-/-) mice develop more severe hepatobiliary damage than male Mdr2(-/-) mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28263455/liver-disease-and-fibrosis-assessment-in-substance-use-related-disorders
#19
Marija Zeremski, Anthony Martinez
Substance users have the highest prevalence of hepatitis C virus (HCV) infection but have rarely been treated, largely because of their mistrust of the health care system, misconceptions about the consequences of the infection, and concerns regarding interferon-related side effects. With the development of highly efficacious, interferon-free therapeutic regimens without significant side effects, the concept of colocating HCV and substance use treatment would appear to be highly feasible. This process has been further facilitated by widespread clinical adaptation of noninvasive assays for fibrosis assessment, which could be performed routinely in substance use treatment facilities...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28263289/establishment-of-a-mouse-model-of-enalapril-induced-liver-injury-and-investigation-of-the-pathogenesis
#20
Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama, Tsuyoshi Yokoi
Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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