Drug induced liver injury - a 2023 update

J Toxicol Environ Health B Crit Rev. 2023 Nov 17;26(8):442-467. doi: 10.1080/10937404.2023.2261848. Epub 2023 Oct 19.

Abstract

Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to as intrinsic, while if the injury occurs spontaneously, it is termed as idiosyncratic. This review predominately focused on idiosyncratic liver injury. The established molecular mechanisms for DILI include (1) mitochondria dysfunction, (2) increased reactive oxygen species levels, (3) presence of elevated apoptosis and necrosis, (4) and bile duct injuries associated with immune mediated pathways. However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown. Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed. The aim of this review was to utilize retrospective cohort studies from across the globe to gain insight into epidemiological patterns. This review considers (1) what is currently known regarding the mechanisms underlying DILI, (2) discusses potential risk factors and (3) implications of the coronavirus pandemic on DILI presentation and research. Future perspectives are also considered and discussed and include potential new biomarkers, causality assessment and reporting methods.

Keywords: DILI causality assessment; Liver; RUCAM; biomarkers; drug-induced liver injury; idiosyncratic DILI.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / etiology
  • Humans
  • Liver Diseases* / epidemiology
  • Retrospective Studies
  • Risk Factors