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  • 标题:Drug-induced liver injury: the dawn of biomarkers?
  • 作者:Stefan Weiler ; Michael Merz ; Gerd A. Kullak-Ublick
  • 期刊名称:F1000 Biology Reports
  • 电子版ISSN:2051-7599
  • 出版年度:2015
  • 卷号:7
  • 页码:1-5
  • DOI:10.12703/P7-34
  • 出版社:Faculty of 1000 Ltd
  • 摘要:Drug-induced liver injury (DILI) is a potentially fatal adverse event with significant medical and economicimpact. Many drugs, especially anti-infective, neurologic or pain-modifying substances, act as hepatotoxins.With cardiovascular toxicity, liver toxicity is one of the two leading causes for drug withdrawal from themarket. The liver can be affected directly, in a predictable and dose-dependentmanner, or idiosyncratically,independent of the dose and therefore unpredictable.Currently DILI is a diagnosis of exclusion that physicians have to bear inmind in patients with an unexplainedincrease of liver enzymes. The type of injury is categorized into hepatocellular, cholestatic, or mixed by therespective enzyme pattern of injury. Symptoms of affected patients can mimic any other liver disease.Therefore, new diagnostic and prognostic biomarkers for early liver injury are currently being evaluated inmulti-centre clinical trials that are conducted by international consortia and other initiatives.Pharmacogenetic testing, next-generation sequencing, proteomics,metabolomics and mechanisticmarkerscan help to preselect susceptible patient populations and tailor drug therapy to individual patients. ProposedDILI indicators that are under investigation include microRNAs, cytokeratin-18 (CK18), high mobilitygroup box protein 1 (HMGB-1), and several other biomarkers. These developments can change clinicalpractice, and improve patients’ safety and management. However, they have not been translated intoclinical practice or approved for routine use yet.Management of DILI usually consists of initial withdrawal ofthe suspected drug and—if applicable—administration of specific antidotes, such as N-acetylcysteine.However, the overall management of DILI could change in the near future with the advent of noveldiagnostic and prognostic DILI markers.
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