Safety of immune checkpoint inhibitors in solid tumor patients with hepatitis C: A real-world analysis.

11158 Background: Patients with hepatitis C virus (HCV) infection are commonly excluded from immune checkpoint inhibitor (ICI) trials. We evaluated hepatotoxicity and outcomes after ICI therapy in patients with versus without HCV. Methods: Retrospective cohort study using the TriNetX Research Network (2014-2024). Adults with solid tumors initiating ICIs were classified as HCV if they had detectable HCV RNA and/or ICD-10 B18.2 (chronic viral hepatitis C) within 1 year prior to ICI start. Cohorts were 1:1 propensity-score matched on demographics, comorbidities, cancer type, metastatic site, and baseline liver tests. Outcomes from day 1–90 after ICI started were ALT ≥150 U/L, total bilirubin ≥3 mg/dL, diagnosis-coded hepatotoxicity, and diagnosis-coded hepatic failure. Overall survival (OS) was assessed for up to 5 years. A sensitivity analysis restricted HCV definition to lab-confirmed HCV RNA (no ICD-10 inclusion). Results: In the primary analysis, 1,157 HCV and 109,309 non-HCV ICI-treated patients were identified; 1,137 patients remained per group after matching. Patients with Hep C had a higher risk of ALT ≥150 U/L, although this did not reach statistical significance (7% vs 5%; p = 0.066). There was no difference in the risk of bilirubin ≥3 mg/dL (5.0% vs 5.0%; p = 1.0). Diagnosis-coded hepatotoxicity was similar (1.8% vs 1.8%; p = 0.875), while diagnosis-coded hepatic failure was higher in the HCV cohort (4.7% vs 2.5%; p = 0.005). Median OS was 20.1 vs 17.2 months (p = 0.0595). In the RNA-only sensitivity analysis (308 matched patients), there was no significant difference in overall survival between patients with and without HCV prior to treatment (27% vs 32%; p = 0.7489). However, the risk of ALT ≥150 U/L was significantly higher in the HCV group (10% vs 5%; p = 0.0058). There was no significant difference in mean bilirubin values after treatment (p = 0.0636). Conclusions: Pre-existing HCV was associated with an increased risk of transaminitis in patients receiving immunotherapy, but there was no statistically significant difference in biliary toxicity or median overall survival. There is also an approximate two-fold increased risk of hepatic failure. These real-world data highlight the importance of closely monitoring for hepatotoxicity in patients receiving immunotherapy and support ICI use in patients with HCV.