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Drug-induced liver disease

Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Hiromitsu Kumada, Hiroshi Miyakawa, Taro Muramatsu, Naoki Ando, Takanori Oh, Kenji Takamori, Hidetomo Nakamoto
AIMS: Patients with chronic liver disease sometimes develop cholestasis, which induces severe whole-body pruritus that may disrupt daily activities and sleep. To determine the efficacy of nalfurafine hydrochloride (5 µg), which is a selective κ-opioid receptor agonist, in improving pruritus, we conducted a double-blind placebo-controlled study in patients with chronic liver disease with refractory pruritus. Nalfurafine hydrochloride at 2.5 µg was also used to evaluate the dose-response relationship...
October 18, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Chun-Yen Liu, Chang-Hung Hsieh, Seung-Hun Kim, Jing-Ping Wang, Yu-Lin Ni, Chun-Li Su, Ching-Fa Yao, Kang Fang
Human liver cancer is one of the most frequently diagnosed cancers worldwide. The development of resistance to therapy limits the application against the disease. To improve treatment, new effective anticancer agents are constantly pursued. Previously, we reported that an indolylquinoline, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), is effective in suppressing the growth of human lung cancer by impairing mitochondria functions. The present study revealed that EMMQ inhibited cell growth and induced apoptosis in liver cancer cells, but not in normal cells...
October 5, 2016: International Journal of Oncology
Yi-Chia Su, Chih-Chien Wu
A 54-year-old woman presented at the emergency department after experiencing lower limb weakness and bilateral ankle pain for 2 days. She had a history of type 2 diabetes mellitus, diabetes mellitus nephropathy with chronic kidney disease, and chronic gouty arthritis. She had received 0.6 mg colchicine orally once or twice daily for 8 months. Four days prior to her emergency department visit, she was discharged from our nephrology ward, where she had been admitted because of a urinary tract infection. During hospitalization, she was treated with intravenous cefazolin for 7 days...
December 2015: Drug Saf Case Rep
Weifeng Li, Yu Wang, Xiumei Wang, Zehong He, Fang Liu, Wenbing Zhi, Hailin Zhang, Xiaofeng Niu
Esculin, a coumarin compound derived from the traditional Chinese herbs such as Cortex Fraxini, has long been used for treating inflammatory and vascular diseases. In present study, we analyzed the role of esculin against macrophages and endotoxin shock induced by lipopolysaccharide (LPS) in mice. Here, we demonstrated that esculin suppressed inflammatory reactions in macrophages and protected mice from LPS-induced endotoxin shock. We found that esculin significantly inhibited the production of nitric oxide (NO) production via the inhibition of nuclear factor-κB (NF-κB) activation in macrophages...
October 13, 2016: European Journal of Pharmacology
Marc Heincelman, Nithin Karakala, Don C Rockey
Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine...
July 2016: Journal of Investigative Medicine High Impact Case Reports
Derrick P McCarthy, Jonathan Woon-Teck Yap, Christopher T Harp, W Kelsey Song, Jeane Chen, Ryan M Pearson, Stephen D Miller, Lonnie D Shea
Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE)...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Elliot B Tapper, Sameer D Saini, Neil Sengupta
BACKGROUND: Many patients have elevated serum aminotransferases reflecting many underlying conditions, both common and rare. Clinicians generally apply one of two evaluative strategies: testing for all diseases at once (non-directed) or just common diseases first (directed). METHODS: We simulated the evaluation of 10,000 adult outpatients with elevated with alanine aminotransferase to compare both testing strategies. Model inputs employed population-based data from the US (National Health and Nutrition Examination Survey) and Britain (Birmingham and Lambeth Liver Evaluation Testing Strategies)...
October 4, 2016: Journal of Hepatology
Sophie Restellini, Olivier Chazouillères, Jean-Louis Frossard
Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders, reported both in Crohn's disease (CD) and ulcerative colitis (UC). They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions. Fatty liver is considered as the most common hepatobiliary complication in IBD whilst primary sclerosing cholangitis (PSC) the most specific one. Less frequently, IBD-associated hepatobiliary disorders include: autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis (PBC), hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, and liver abscess...
October 6, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Laura Lucarini, Mariaconcetta Durante, Cecilia Lanzi, Alessandro Pini, Giulia Boccalini, Laura Calosi, Flavio Moroni, Emanuela Masini, Guido Mannaioni
Idiopathic pulmonary fibrosis is a severe disease characterized by excessive myofibroblast proliferation, extracellular matrix and fibrils deposition, remodelling of lung parenchyma and pulmonary insufficiency. Drugs able to reduce disease progression are available, but therapeutic results are unsatisfactory; new and safe treatments are urgently needed. Poly(ADP-ribose) polymerases-1 (PARP-1) is an abundant nuclear enzyme involved in key biological processes: DNA repair, gene expression control, and cell survival or death...
October 4, 2016: Journal of Cellular and Molecular Medicine
Ren-Jie Lu, Yan Zhang, Feng-Lei Tang, Zhong-Wei Zheng, Zheng-Da Fan, Shan-Mei Zhu, Xian-Feng Qian, Na-Na Liu
Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory-specific serological markers. In this study, we comprehensively assessed the clinical characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes concerning DILI, and explored the similarities in mechanisms between Chinese and Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for systematic retrospective study...
October 2016: Experimental and Therapeutic Medicine
Ángel Brea, Xavier Pintó, Juan F Ascaso, Mariano Blasco, Ángel Díaz, Pedro González-Santos, Antonio Hernández-Mijares, Teresa Mantilla, Jesús Millán, Juan Pedro-Botet
Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality...
September 27, 2016: Clínica e Investigación en Arteriosclerosis
Kathleen M Gura, Andrew E Mulberg, Paul D Mitchell, John Yap, Clara Y Kim, Minjun Chen, Alexis Potemkin, Mark Puder
BACKGROUND: Intestinal failure-associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug-induced liver injury (DILI), those diagnostic criteria could potentially be used in this population...
September 28, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
Jun Yang, Ya-Li Yu, Yu Jin, Ying Zhang, Chang-Qing Zheng
AIM: To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS: A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type)...
September 7, 2016: World Journal of Gastroenterology: WJG
Li-Li Gong, Guang-Run Li, Wen Zhang, He Liu, Ya-Li Lv, Fei-Fei Han, Zi-Rui Wan, Ming-Biao Shi, Li-Hong Liu
Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing. However, there is a lack of appropriate drugs for the therapy of NAFLD. In the present article, we aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD on ob/ob mice and BRL cells. ASD significantly decreased hepatic steatosis and heptocyte apoptosis in ob/ob mice. Furthermore, ASD significantly activated the autophagic flux assessed by decreased the expression of LC3-II, p62 accumulation of autophagosomes...
September 26, 2016: Journal of Pharmacology and Experimental Therapeutics
Arijit Mondal, Tanmoy Guria, Tapan Kumar Maity, Anupam Bishayee
Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus-(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2)...
2016: International Journal of Molecular Sciences
Volker M Lauschke, Delilah F G Hendriks, Catherine C Bell, Tommy B Andersson, Magnus Ingelman-Sundberg
The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity...
September 23, 2016: Chemical Research in Toxicology
Nalini Mishra, V N Mishra, Parineeta Thakur
INTRODUCTION: Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. MATERIAL AND METHOD: Eighty pregnant women with abnormal liver dysfunction were studied prospectively...
October 2016: Journal of Obstetrics and Gynaecology of India
Einar S Björnsson, Jiezhun Gu, David E Kleiner, Naga Chalasani, Paul H Hayashi, Jay H Hoofnagle
OBJECTIVE: The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. BACKGROUND: Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. METHODS: Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. RESULTS: Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%)...
June 14, 2016: Journal of Clinical Gastroenterology
Cui Yang, Si-Dao Zheng, Hong-Jin Wu, Shao-Jun Chen
OBJECTIVE: MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis. DATA SOURCES: Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms "microRNA", "miR", "transforming growth factor β", "tgf β", "mitogen-activated protein kinase", "mapk", "integrin", "p38", "c-Jun NH2-terminal kinase", "jnk", "extracellular signal-regulated kinase", "erk", and "fibrosis"...
2016: Chinese Medical Journal
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