Impact of Hepatitis C Viremia on Overall Survival and Hepatic Decompensation Among Patients with Unresectable Hepatocellular Carcinoma Receiving Immunotherapy

INTRODUCTION: Hepatitis C (HCV) is associated with an immunosuppressive liver microenvironment, but whether HCV affects immune checkpoint inhibitor (ICI) outcomes in unresectable hepatocellular carcinoma (HCC) remains unknown. METHODS: We performed a single-center retrospective cohort study of patients with unresectable HCC treated with ICIs. In patients with a history of HCV, viremia was defined as a detectable viral load before immunotherapy. The primary outcome was overall survival (OS); secondary outcomes were real-world progression-free survival (PFS), time on treatment, and time to hepatic decompensation. RESULTS: Among 350 patients with unresectable HCC treated with ICIs, 135 (39%) had a history of HCV, of which 37 (27%) were viremic. Viremia was not associated with OS (hazard ratio [HR] 0.88, 95% CI 0.53-1.44, P = 0.600), but was associated with longer real-world PFS (HR 0.59, 95% CI 0.36-0.96, P = 0.033) and longer time on treatment (HR 0.63, 95% CI 0.40-0.99, P = 0.044). Compared with patients with non-HCV related unresectable HCC (n = 215), viremic patients had longer real-world PFS (HR 0.65, 95% CI 0.44-0.97, P = 0.037) but nonviremic patients did not (HR 0.87, 95% CI 0.66-1.17, P = 0.359). Viremia was not associated with time to hepatic decompensation (HR 1.11, 95% CI 0.61-2.04, P = 0.728), but in patients who survived at least 1 year without decompensating, viremia was associated with shorter time to decompensation (29.8 months vs median not reached, log-rank P = 0.010). DISCUSSION: Viremia was not associated with OS among ICI-treated HCV patients with unresectable HCC, but was associated with longer real-world PFS and time on treatment. Further studies are needed to investigate these findings.