Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management

  • HK Björnsson
    Correspondence
    Corresponding author at: Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Affiliations
    Sahlgrenska University Hospital, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Gothenburg Sweden
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  • ES Björnsson
    Affiliations
    Landspitali - The National University Hospital of Iceland, Section of Gastroenterology and Hepatology, Reykjavik, Iceland

    Faculty of Medicine University of Iceland, Reykjavik, Iceland
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Published:November 09, 2021DOI:https://doi.org/10.1016/j.ejim.2021.10.035

      Highlights

      • Drug induced liver injury can be caused by a myriad of different medications in addition to herbal and dietary supplements.
      • The severity of DILI can range from asymptomatic mild liver enzyme elevations to liver failure and death.
      • Immune-mediated liver injury is becoming more prevalent with increased use of checkpoint-inhibitors and other biologic medications which affect the equilibrium of the immune system.
      • It is important that physicians have the tools to diagnose suspected DILI cases, exclude other causes and manage patients with DILI.
      • It is important in the future to develop new biomarkers for physicians to use in the diagnosis of DILI, that can distinguish suspected DILI cases from other causes of liver injury.

      Abstract

      Drug-induced liver injury (DILI) is an important but rare adverse event which can range from mild liver enzyme elevations to liver failure, transplantation or death. A large proportion of commonly used medications, in addition to herbal and dietary supplements, can cause liver injury. DILI has been categorized as direct or idiosyncratic but indirect liver injury has emerged as a third type of drug-induced liver injury. These types of liver injury may warrant different clinical approach and treatment. Associations of HLA genotypes and risk of DILI have highlighted the importance of the immune system in the pathogenesis of DILI. Furthermore, novel agents affecting the immune response can lead to liver injury, often associated with autoimmune features in serologic tests and liver biopsies. Overall, the diagnosis of DILI remains a challenge as it is requires detailed case evaluation in addition to reviewing the hepatotoxic potentials and clinical signatures of the implicated agents. Biochemical profiles vary between agents and although individual drugs tend to portray a consistent clinicopathologic signature, many drugs have multiple signatures. Thanks to multicenter prospective studies on DILI and websites in the public domain such as LiverTox, physicians are provided with tools to investigate suspected DILI cases to increase the likelihood of establishing adiagnosis. The pathogenesis of DILI, epidemiology and current challenges in the diagnosis and management of the disease are reviewed in the paper.

      Keywords

      Abbreviations:

      AIH (Autoimmune hepatitis), ALP (Alkaline phophatase), ALT (Alanine aminotransferase), ANA (Anti-nuclear antibody), AST (Aspartate aminotransferase), DIAIH (Drug-induced autoimmune hepatitis), DILI (Drug-induced liver injury), NAC (N-acetylcysteine), NAFLD (Nonalcoholic fatty liver disease), RUCAM (Roussel-Uclaf Causality Assessment Method), SMA (Anti-smooth muscle antibody), SOS (Sinusoidal obstruction syndrome), ULN (Upper limit of normal)
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