Drug-induced liver injury in inflammatory bowel disease: Challenges in diagnosis and monitoring

Drug-induced liver injury (DILI) is an important but often underrecognized complication in the management of inflammatory bowel disease (IBD), particularly in patients receiving long-term immunomodulatory or biologic therapies. Agents such as thiopurines, methotrexate, anti-tumor necrosis factor agents, and newer small molecules including tofacitinib and upadacitinib have all been implicated in hepatotoxicity, with clinical manifestations ranging from asymptomatic elevations in liver enzymes to severe hepatic injury. Differentiating DILI from hepatobiliary disorders commonly associated with IBD, such as primary sclerosing cholangitis, metabolic dysfunction-associated steatotic liver disease, and autoimmune hepatitis, remains a significant diagnostic challenge. The absence of standardized monitoring protocols, coupled with the variable latency and heterogeneous presentation of DILI, further complicates early recognition and management. In this narrative review, we synthesize current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of DILI in IBD. We also outline diagnostic strategies, including the role and limitations of causality assessment tools, and propose practical considerations for baseline evaluation, longitudinal monitoring, and therapeutic decision-making.