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

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.