Hepatobiliary Adverse Events Linked to Immune Checkpoint Inhibitors: A Real-World Pharmacovigilance Analysis Using FAERS Data.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but cause significant hepatobiliary toxicity (e.g., liver dysfunction, immune-mediated liver disease). Prior studies were limited to small samples or case reports. This study evaluated hepatobiliary toxicity, risk variations, and temporal trends for six ICIs (PD-1/PD-L1 inhibitors) via the FDA Adverse Event Reporting System (FAERS) to guide safer use. METHODS: We analyzed 18 640 061 FAERS reports (2004-2024). Disproportionality analyses (ROR, PRR, EBGM, BCPNN) detected hepatobiliary toxicity signals. A Weibull model analyzed AE timing. Logistic regression assessed effects of age, gender, and weight. RESULTS: PD-L1 inhibitors (Durvalumab, Atezolizumab) are associated more strongly with immune-mediated liver disease/hepatic failure (ROR = 4.28-5.07). PD-1 inhibitors (Nivolumab, Pembrolizumab) are linked more to hepatitis/liver abnormalities (ROR = 3.42-3.93). AE reports are common in males (53.32%) and patients > 65 years (43.43%), though demographics didn't alter risk (p > 0.05). Median onset: 23 days (Toripalimab liver injury) vs. 84 days (Tislelizumab autoimmune hepatitis), supporting drug-specific monitoring in the first three months. CONCLUSION: Our FAERS analysis showed PD-L1 inhibitors were more associated with immune-mediated liver disease and hepatic failure, whereas PD-1 inhibitors were linked to hepatitis and liver abnormalities, underscoring the need for drug-specific monitoring.