A Practical Approach to Abnormal Liver Enzymes in Pediatric IBD in the Biologic and Targeted Therapy Era

Inflammatory bowel disease (IBD) is increasingly diagnosed in children and adolescents, and abnormal liver enzymes are a common yet often underrecognized clinical challenge. In the era of biologic and targeted therapies, liver test abnormalities may reflect drug-induced liver injury (DILI), hepatobiliary manifestations of IBD such as primary sclerosing cholangitis (PSC), autoimmune liver disease, infection, metabolic dysfunction-associated steatotic liver disease (MASLD), or reactive inflammatory changes. Timely recognition of the underlying etiology is essential to avoid unnecessary treatment interruption while preventing progression of clinically significant liver disease. We performed a narrative review of the current literature and synthesized available evidence to develop a practical, clinically oriented approach for the evaluation and management of abnormal liver enzymes in pediatric patients with IBD receiving biologic and advanced therapies. Interpretation of abnormal liver enzymes requires integration of the biochemical pattern of injury, temporal relationship to medication exposure, disease activity, and patient-specific risk factors. Hepatocellular, cholestatic, and mixed patterns of injury provide an initial framework for targeted evaluation and help differentiate DILI from PSC, autoimmune hepatitis (AIH), AIH-PSC overlap syndrome, infectious hepatitis, and other etiologies. Biologic and targeted therapies exhibit distinct hepatic safety profiles, necessitating individualized monitoring strategies. A stepwise evaluation incorporating laboratory assessment, imaging, and selective liver biopsy can facilitate accurate diagnosis, guide management decisions, and identify patients requiring hepatology referral.