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 inhibitors (ICIs)-related trials in hepatocellular carcinoma (HCC) have strict restrictions on HBV DNA load because of HBV reactivation. This study aimed to compare the HBV reactivation between HCC patients with low or high HBV DNA loads receiving ICIs and antiviral therapy. Patients and Methods: This prospective observational study (NCT04680598) recruited HBsAg-positive HCC patients 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 HBeAg positivity (24.1% vs 7.0%, p < 0.001), ALBI grade 2-3 (49.9% vs. 33.7%, p < 0.001), and BCLC stage C (83.3% vs. 72.5%, p < 0.001). The HBV reactivation rate (4.5% vs. 6.1%, relative risk, 1.24; 95% CI: 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 significantly difference in the risk of HBV reactivation between HCC patients with HBV DNA ≤ 500 IU/ml or HBV DNA > 500 IU/ml when treated with ICIs and concurrent antiviral prophylaxis.