Interaction between HBsAg response and the prognosis of patients with HBV-associated HCC receiving anti-PD-1/PD-L1

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are widely used in advanced hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is a major etiology of HCC, yet predictive biomarkers for anti-PD-1/PD-L1 efficacy in HBV-related HCC (HBV-HCC) remain scarce. This retrospective study analyzed 76 patients with HBV-HCC treated at Nanjing Medical University Affiliated Taizhou People’s Hospital (2019–2023). Demographic, biochemical, and serial Hepatitis B surface antigen (HBsAg) data were collected. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included HBV reactivation and hepatitis. Statistical analyses involved t-tests, chi-square tests, and Kaplan–Meier with log-rank tests. All patients were HBsAg-positive and received antiviral therapy. Groups were divided based on anti-PD-1/PD-L1 treatment, with the treatment group further subclassified by increasing or decreasing HBsAg trends. Baseline characteristics showed no significant differences. The anti-PD-1/PD-L1 group exhibited significantly longer PFS (P < 0.001) and OS (P = 0.039). Within the treatment group, decreasing HBsAg was associated with improved OS (P = 0.027). HBV reactivation rates showed no significant difference, nor did HBV-associated hepatitis (4.7% vs. 9.1%; 4.65% vs. 3.03%). A decline in HBsAg may indicate better treatment response and survival in HBV-HCC patients receiving PD-1/PD-L1 inhibitors, without increasing HBV reactivation or hepatitis risk, supporting its safety. PD-1/PD-L1 inhibitors may promote HBsAg reduction, though further studies are needed to clarify the mechanisms.