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

Abstract

Abstract Background:The use of programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors has become widespread in the treatment of advanced hepatocellular carcinoma (HCC). However, the role of hepatitis B virus( HBV) as a major pathogenic factor in HCC has garnered significant attention regarding the efficacy of anti-PD-1/PD-L1 therapy for HBV-related HCC(HBV-HCC), yet effective predictive biomarkers remain lacking. Method: The present study retrospectively collected data from 76 patients with HBV-HCC who were diagnosed and treated at Taizhou People's Hospital Affiliated to Nanjing Medical University between January 2015 and August 2023. The collected data included demographic characteristics and blood biochemical parameters, while the levels of hepatitis B surface antigen(HBsAg) during treatment were also recorded. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS), while the secondary endpoints included HBV reactivation and associated hepatitis. Continuous variables were compared using independent sample t-tests, categorical variables were compared using chi-square tests, and overall survival was analyzed using Kaplan-Meier curves and log-rank tests.All patients tested positive for serum HBsAg prior to treatment and had received antiviral therapy. After excluding confounding factors, the patients were categorized into two groups based on their receipt of anti-PD-1/PD-L1 therapy: the experimental group (administered with anti-PD-1/PD-L1) and the control group (not administered with anti-PD-1/PD-L1). The experimental group was further divided into two subgroups: the subgroup exhibiting increasing levels of HBsAg and the subgroup displaying decreasing levels of HBsAg. Result: A total of 76 patients with HBV-HCC were enrolled in this study. The general information between the two groups was compared, and no statistically significant difference was observed (P>0.05). However, there were significant statistical differences in PFS and OS between the experimental group and the control group (t=5.062, p<0.001; p=0.039<0.05, respectively). The subgroup analysis conducted within the experimental group further revealed a statistically significant difference in OS (p=0.027<0.05). Moreover, HBV reactivation occurred without any significant difference observed in the incidence rates of HBV-associated hepatitis (4.7% vs 9.1% and 4.65% vs 3.03%, respectively). Conclusion:In patients with HBV-HCC undergoing PD-1/PD-L1 inhibitor treatment, a decline in HBsAg levels can potentially serve as an indicator of enhanced tumor response and prolonged survival, while also not increasing the incidence of HBV reactivation and liver damage, thereby highlighting favorable safety profiles. Our study further suggests that PD-1/PD-L1 inhibitors may facilitate the reduction in HBsAg levels; however, additional investigations are warranted to elucidate the underlying mechanisms.