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.