Immune Checkpoint Inhibitor-Induced Rapid Decline in Hepatitis B Virus Markers Improves the Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma Patients

BACKGROUND: Limited research exists on immune checkpoint inhibitors (ICIs)' antiviral efficacy in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of ICIs on multiple HBV markers and its correlation with HCC prognosis. METHODS: A retrospective cohort study was performed on 318 HBV-related HCC patients, including 268 who received ICIs (with/without targeted therapy; ICI group) and 50 who received targeted therapy alone (non-ICI group). Levels of quantitative HBsAg (qHBsAg), HBV DNA, HBV RNA, and HBcrAg were monitored. Tumor response was evaluated using RECIST 1.1. RESULTS: Over a median 8.1-month follow-up, the ICI group showed a significantly greater decrease in all HBV markers. At week 96, the ICI group showed significantly higher cumulative incidences of HBsAg response (loss or ≥0.5 Log10 decline) (41.6% vs 14.9%, P = .006) and HBcrAg response (negativity or ≥1 Log10 decline) (46.3% vs 18.1%, P = .007) than non-ICI group and a significantly faster achievement rate of HBV RNA response (negativity or ≥0.5 Log10 decline) (hazard ratio [HR]: 1.80, 95% CI: 1.08-2.99, P = .021). Notably, the PD-1 inhibitors showed significantly better virological response efficacy than PD-L1 inhibitors (HR = 2.04-5.43). The patients with lower levels of HBV markers at enrollment demonstrated significantly better overall survival. Moreover, patients achieving virological response were associated with significantly better survival outcomes and tumor response, with HR ranging 1.64-8.06. CONCLUSIONS: Immune checkpoint inhibitors demonstrate dual therapeutic effects in HBV-related HCC, significantly reducing multiple HBV markers while concurrently enhancing prognosis in combination with antiviral therapy, emphasizing the importance of sustained virological suppression for optimal HCC outcomes.