HBV Reactivation in Patients with Hepatocellular Carcinoma Treated with PD-1/-L1 Antibodies and Concurrent Antiviral Prophylaxis Agents: A Prospective Observational Study

PURPOSE: Immune checkpoint inhibitor (ICI)-related trials in hepatocellular carcinoma (HCC) have strict restrictions on hepatitis B (HBV) DNA load because of HBV reactivation. This study aimed to compare the HBV reactivation between patients with HCC with low or high HBV DNA loads receiving ICIs and antiviral therapy. PATIENTS AND METHODS: This prospective observational study (NCT04680598) recruited hepatitis B surface antigen-positive patients with HCC who received concurrent antiviral therapy with initial ICI treatment. Participants were divided into HBV DNA-low (≤500 IU/mL) and HBV DNA-high (>500 IU/mL) groups. The primary endpoint was the HBV reactivation rate. RESULTS: Between December 25, 2020, and February 23, 2024, 356 and 659 participants were enrolled in the HBV DNA-low and HBV DNA-high groups. The HBV DNA-high group included significantly higher proportions of patients with hepatitis Be antigen positivity (24.1% vs. 7.0%, P < 0.001), albumin-bilirubin grade 2 to 3 (49.9% vs. 33.7%, P < 0.001), and Barcelona Clinic Liver Cancer stage C (83.3% vs. 72.5%, P < 0.001). The HBV reactivation rate (4.5% vs. 6.1%, relative risk, 1.24; 95% confidence interval, 0.81-1.89; P = 0.29), frequencies of HBV reactivation-associated hepatitis (1.7% vs. 2.3%, P = 0.53), and interruptions in ICI treatment (25.8% vs. 30.5%, P = 0.12) were comparable in the HBV DNA-low group and HBV DNA-high group. CONCLUSIONS: There was no significant difference in the risk of HBV reactivation between patients with HCC with HBV DNA ≤500 IU/mL and those with HBV DNA >500 IU/mL when treated with ICIs and concurrent antiviral prophylaxis.