The contemporary epidemiology, causes, and management of drug-induced liver injury.

Abstract

Drug-induced liver injury is an important cause of clinically significant liver disease. In Western countries, antibiotics are the leading cause of DILI, with amoxicillin-clavulanate and trimethoprim-sulfamethoxazole most frequently implicated. Herbal and dietary supplements (HDS) are increasingly implicated as a cause of DILI worldwide, including ashwagandha, turmeric, and green tea extract in the United States. Advances in DILI diagnosis include the development of the Revised Electronic Causality Assessment Method (RECAM) instrument and the creation of the LiverTox website with drug and HDS likelihood scores. Newer causes of DILI include kinase inhibitors for cancer and autoimmune conditions, various immunomodulatory agents, and medications to treat liver disease. Immune-mediated liver injury from checkpoint inhibitors (ILICI) typically presents within the first 6 months of treatment with asymptomatic laboratory abnormalities. Treatment of DILI remains primarily supportive by withholding the offending agent and close monitoring, with corticosteroids only showing benefit in highly selected patients. Over 80% of DILI patients will fully recover within 6 months of drug discontinuation with supportive care, but recent outcomes for DILI-related ALF due to HDS have been worsening. Prognostic models can help identify hospitalized DILI patients in need of transplant and others who are at increased risk for 6-month mortality. Whole-exome sequencing to identify new genetic risk factors, development of in vitro diagnostic assays, and further studies of the host adaptive immune response in DILI pathogenesis will hopefully lead to further improvements in DILI diagnosis and treatment.