Drug-Induced Liver Disease

Drug-induced liver injury (DILI) encompasses a spectrum of liver diseases from acute and chronic hepatitis, cholestatic syndromes, and vascular lesions through to benign and malignant liver neoplasms. Idiosyncratic drug reactions constitute the majority of cases. Newer agents associated with DILI include tyrosine kinase and tumor necrosis factor α inhibitors, while telithromycin, troglitazone, and ximelagatran have been withdrawn due to hepatotoxicity. A variety of drug- and host-related characteristics are associated with DILI. Of the latter, pharmacogenetic factors are becoming increasingly relevant (e.g., flucloxacillin- and amoxicillin-clavulanate-associated liver injury with specific HLA alleles; valproic acid and mitochondrial DNA repair-related gene POLG1 polymorphisms). Interactions between drugs and other liver diseases (e.g., antituberculous drugs and viral hepatitis B and C; tamoxifen and nonalcoholic fatty liver disease) are also now better characterized. Acetaminophen is the leading cause of acute liver failure in the United States. N-acetylcysteine remains the only antidote available for such cases and is also of value in the setting of acute liver failure from drugs other than acetaminophen. Immediate cessation of the offending drug and supportive care, along with corticosteroids, ursodeoxycholic acid, and liver transplantation in selected cases, is critical to improving outcomes of patients with DILI.