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Drug induced liver injury

Beverley Kok, Erica L W Lester, William M Lee, A James Hanje, R Todd Stravitz, Safwat Girgis, Vaishali Patel, Joshua R Peck, Christopher Esber, Constantine J Karvellas
BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014...
March 21, 2018: Digestive Diseases and Sciences
Tianhua Fu, Shijie Wang, Jinping Liu, Enbo Cai, Haijun Li, Pingya Li, Yan Zhao
The purpose of this study was to evaluate the protective effects of α-mangostin against acetaminophen (APAP)-induced acute liver injury and discover its potential mechanisms in mice. Mice were continuously treated with α-mangostin (12.5 and 25mg/kg) by intragastric administration once daily for 6 days, and injected intraperitoneally with APAP (300mg/kg) after 1h of α-mangostin administration on the last day. After APAP exposure for 24h, the liver and serum were gathered to evaluate the hepatotoxicity. The results showed that α-mangostin effectively decreased the serum levels of alanine aminotransferase, aspartate transaminase, tumor necrosis factor (TNF-α), interleukin-1β and 6 (IL-1β, IL-6), and hepatic malondialdehyde level; and recovered hepatic glutathione (GSH), superoxide dismutase and catalase activities...
March 18, 2018: European Journal of Pharmacology
Javier Martínez-Casanova, Nuria Carballo, Sonia Luque, Luisa Sorli, Santiago Grau
Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range...
2018: Infection and Drug Resistance
Xianxun Shi, Huiyuan Bai, Ming Zhao, Xiaorong Li, Xianchao Sun, Hongbo Jiang, Ailing Fu
Drug-induced liver injury shares a common feature of mitochondrial dysfunction. Mitochondrial therapy (mitotherapy), which replaces malfunctional mitochondria with functional exogenous mitochondria, may be a fundamental approach for treating drug-mediated hepatotoxicity. Here, we suggested that mitochondria isolated from human hepatoma cell could be used to treat acetaminophen (APAP)-induced liver injury in mice. When the mitochondria were added into the cell media, they could enter primarily cultured mouse hepatocyte...
March 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Salvatore Sutti, Frank Tacke
Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...
March 15, 2018: Clinical Science (1979-)
K Isoda, T Nozawa, Y Taira, I Taira, Y Shimizu, I Ishida
Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury...
March 5, 2018: Die Pharmazie
Jia-Bo Wang, Yun Zhu, Zhao-Fang Bai, Fu-Sheng Wang, Xiu-Hui Li, Xiao-He Xiao
Herb-induced liver injury (HILI) is a type of adverse drug reactions related to using Chinese medicine (CM) or herbal medicine (HM), and is now a growing segment of drug-induced liver injury (DILI) worldwide. Owing to the complicated compositions and miscellaneous risk factors associated with the clinical usage of CM or HM, it is more challenging to diagnose and manage HILI than DILI. In the present guideline issued by the China Association of Chinese Medicine (CACM), the authors present an evidence chain-based workflow with 9 structured judgment criteria for diagnosing HILI...
March 15, 2018: Chinese Journal of Integrative Medicine
Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
James B Leonard, Kashif M Munir, Hong K Kim
Metoclopramide (MCP) is a commonly used anti-emetic in the emergency department (ED). Its use is generally well tolerated; although infrequent adverse reactions such as extrapyramidal reactions or tardive dyskinesia are reported. However, many ED providers are not familiar with the potentially life-threatening hypertensive emergency that can be precipitated by MCP administration in patients with pheochromocytoma. A previously healthy 36-year-old woman presented to the ED with headache and nausea. She developed acute hypertensive emergency (acute agitation, worsening headache, chest pain and wide complex tachycardia) when her blood pressure (BP) increased to 223/102mmHg (initial BP, 134/86mmHg) after receiving intravenous MCP...
March 5, 2018: American Journal of Emergency Medicine
Lucy Meunier, Jose Ursic-Bedoya, Georges-Philippe Pageaux, Dominique Larrey
BACKGROUND: Although very rare, pantoprazole can result in acute hepatitis. It has yet to be reported, however, that it can also cause chronic autoimmune hepatitis. AIM, METHOD, AND RESULTS: We report the case of a patient in whom pantoprazole administration for two months was followed by acute liver injury with severe jaundice and features of autoimmunity. A liver biopsy revealed acute hepatocellular lesions associated with cholestasis, acute cholangitis, and polymorphous inflammatory infiltration suggestive of drug-induced liver injury...
March 12, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Peng Sun, Jing-Jie Zhu, Ting Wang, Qi Huang, Yu-Ren Zhou, Bang-Wei Yu, Hua-Liang Jiang, He-Yao Wang
As a widely used anti-gout drug, benzbromarone has been found to induce hepatic toxicity in patients during clinical treatment. Previous studies have reported that benzbromarone is metabolized via cytochrome P450, thus causing mitochondrial toxicity in hepatocytes. In this study, we found that benzbromarone significantly aggravated hepatic steatosis in both obese db/db mice and high fat diet (HFD)-induced obese (DIO) mouse models. However, benzbromarone had less effect on the liver of lean mice. It was found that the expression of mRNAs encoding lipid metabolism and some liver-specific genes were obviously disturbed in benzbromarone-treated DIO mice compared to the control group...
March 8, 2018: Biochimica et Biophysica Acta
Michael Schloss, Daniel Becak, Sebastian T Tosto, Arash Velayati
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin...
March 10, 2018: American Journal of Case Reports
David Noiva Perdigoto, Pedro Amaro, Manuela Ferreira, Luis Tomé
A patient is admitted with complaints of recent onset nausea, discomfort, jaundice and blood tests that reveal severe hepatitis. At the time, she had been taking medication with Hypericum perforatum (St John's wort) for 6 months, and 6 weeks before this event, she took flupirtine maleate. A few days after being admitted, she developed encephalopathy progressing to acute liver failure (ALF) requiring unsuccessful liver transplantation. The patient was ultimately diagnosed with drug-induced liver injury (DILI)...
March 9, 2018: BMJ Case Reports
Alamgeer, Zain Nasir, Muhammad Naeem Qaisar, Ambreen Malik Uttra, Haseeb Ahsan, Kifayat Ullah Khan, Ikram Ullah Khan, Muhamamd Saleem, Khadijai, Hira Asif, Amber Sharif, Waqas Younis, Huma Naz
Hepatic diseases are becoming common day by day and pose serious health threats to the life of humans. In order to treat these diseases, the attention of man is diverting towards herbal drugs, which are much safer and cost effective than synthetic drugs. The aim of present study was to investigate hepatoprotective activity of methanolic extract of Melilomus officinalis against paracetamol and carbon tetrachloride induced hepatic damage. Melilotus officinalis at selected oral doses of 50 mg/kg and 100 mg/kg showed significant hepatoprotective effects by decreasing the levels of serum marker enzymes such as total bilirubin, SGOT, SGPT, ALP, albumin and total protein, when compared with standard drug (silymarin) and negative control...
May 2017: Acta Poloniae Pharmaceutica
Shiho Makabe, Toshio Mochizuki, Michihiro Mitobe, Yumi Aoyama, Hiroshi Kataoka, Ken Tsuchiya, Kosaku Nitta
BACKGROUND: In 2014, tolvaptan, a vasopressin receptor antagonist, was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD) in Japan. Clinical trials of tolvaptan revealed frequent occurrence of the liver function abnormality. According to the package insert in Japan, liver function tests should be performed once a month in patients receiving tolvaptan. Furthermore, immediate discontinuation of tolvaptan is recommended in the appearance of liver function abnormalities...
March 5, 2018: Clinical and Experimental Nephrology
Henrik Cordes, Christoph Thiel, Vanessa Baier, Lars M Blank, Lars Kuepfer
Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism...
2018: NPJ Systems Biology and Applications
Clement Bresteau, Sophie Prevot, Gabriel Perlemuter, Cosmin Voican
Drug-induced liver injury is the fourth most common cause of liver disease in industrialised countries. Methylprednisolone is often considered to be a treatment with a low hepatotoxicity. We report a case of methylprednisolone-induced liver injury in a 35-year-old woman. She was admitted to our department for acute liver injury 2 months after a treatment with high dose of methylprednisolone (1 g/day) for a multiple sclerosis relapse. No other cause of liver injury could be found (screening for hepatotropic viruses, autoimmune antibodies, ceruloplasmin, abdominal ultrasonography and liver biopsy)...
March 5, 2018: BMJ Case Reports
Gaby Danan, Rolf Teschke
Launched in 1993 and partially based on the results of an international consensus meeting organized under the auspices of the Council of International Organizations of Medical Sciences (CIOMS), the Roussel Uclaf Causality Assessment Method (RUCAM) is the most used causality assessment tool worldwide for the diagnosis of drug-induced liver injury (DILI) and herb-induced liver injury (HILI) in a large number of epidemiological studies, case reports, and case series. The 25-year experience of RUCAM use confirmed that the success was due to its objective, standardized, and liver-injury-specific approach structured with defined key elements derived from a series of DILI cases with positive rechallenge...
March 3, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Steven Wink, Steven W Hiemstra, Suzanne Huppelschoten, Janna E Klip, Bob van de Water
Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of DILI liability: SRXN1-GFP (oxidative stress), CHOP-GFP (ER stress/UPR response), p21 (p53-mediated DNA damage-related response) and ICAM1 (NF-κB-mediated inflammatory signaling)...
March 3, 2018: Archives of Toxicology
Fumihiko Nagano, Tomohiro Mizuno, Shuji Mizumoto, Kengo Yoshioka, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Shuhei Yamada, Tadashi Nagamatsu
Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones...
February 28, 2018: European Journal of Pharmacology
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