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Diagnosis, management and prevention of drug-induced liver injury
  1. S Verma1,
  2. N Kaplowitz2
  1. 1
    Department of Medicine, Brighton and Sussex Medical School, Brighton, UK
  2. 2
    USC Research Centre for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, USA
  1. Correspondence to Dr N Kaplowitz, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033, USA; kaplowit{at}usc.edu

Abstract

Drug-induced liver injury (DILI) is increasingly being recognised as a significant cause of both acute and chronic liver disease. The most commonly implicated agents are paracetamol, antimicrobials, non-steroidal anti-inflammatory drugs, statins, isoniazid and herbal remedies. Drug-induced hepatotoxicity is generally idiosyncratic in nature. The pathogenesis of DILI remains enigmatic, but involves exposure to the toxic agent, mitochondrial injury, failure of adaptation, and innate and adaptive immune responses. Diagnosis of drug-induced liver diseases can be difficult, but the key to causality is to diligently exclude other causes of liver injury, and to identify a characteristic clinical drug-related signature. Management of drug-induced liver injury is symptomatic, with early referral to a liver transplant unit at the first hint of liver failure, especially in those with non-paracetamol-induced liver injury. Prevention of drug hepatotoxicity includes increased vigilance during pre-clinical drug development and clinical trials, alanine aminotransferase monitoring with certain drugs, better marketing strategies, and the future identification of both diagnostic and prognostic biomarkers.

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Footnotes

  • Competing interests SV: none. NK: consults for GlaxoSmithKline, JNJ, King Pharmaceuticals, TEVA, Pfizer, Bristol Myers Squibb, Daiichi Sankyo, ISIS Pharm, Hepregen, Eisai Medical Research, Entelos, Merck, Gilead, Allergan, Amgen, Novartis, Roche, Sanofi-Aventis, Wyeth and Cougan Pharmaceuticals regarding liver safety.

  • Provenance and Peer review Not commissioned; externally peer reviewed

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