Drug induced liver injury: an update

• Published in: Archives of toxicology 2020-10, Vol.94 (10), p.3381-3407
• Main Authors: Garcia-Cortes, Miren, Robles-Diaz, Mercedes, Stephens, Camilla, Ortega-Alonso, Aida, Lucena, M. Isabel, Andrade, Raúl J.
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers; Biomedical and Life Sciences; Biomedicine; Causality; Cholestasis; Clinical trials; Corticoids; Corticosteroids; Diet; Dietary supplements; Drug metabolism; Drugs; Environmental Health; Environmental risk; Hepatotoxicity; Immune checkpoint inhibitors; Immune response; Immune system; Immunosuppressive agents; Liver; Liver diseases; Necrosis; Occupational Medicine/Industrial Medicine; Oxidative stress; Pharmacology/Toxicology; Phenotypes; Review Article; Risk analysis; Risk factors; Ursodeoxycholic acid
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-020-02885-1

Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors.