Relationship between HBsAg/HBV DNA and prognosis in patients with HBV-related hepatocellular carcinoma treated with PD-1/PD-L1 inhibitors.

Objectives: Blocking the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis could reverse the immune tolerance in the liver microenvironment of hepatocellular carcinoma (HCC). We investigated the efficacy and the safety of PD-1/PD-L1 inhibitors and the possibility of hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV) DNA levels as prognostic biomarkers in patients with HBV-related HCC.

Design: A retrospective study.

Methods: We retrospectively analyzed patients with HBV-related HCC and positive quantitative HBsAg (qHBsAg) who received PD-1/PD-L1 inhibitor therapy at least once. The primary endpoints were overall survival (OS) and objective response rate (ORR), with the secondary endpoint being disease control rate (DCR). Cox regression models were used to illustrate the association of patient characteristics with survival.

Results: A total of 235 patients with HBV-related HCC were included in this study. The median OS for all patients was 20.9 months. The ORR and DCR were 15.7% and 70.6%, respectively. Baseline HBV DNA levels were associated with DCR (p = 0.004). Patients in the qHBsAg-response group in the fourth week had a longer OS after PD-1/PD-L1 inhibitor treatment compared to those in the qHBsAg nonresponse group (29.1 months vs 14.9 months, p = 0.04). Multivariate Cox regression analysis suggested that positive baseline HBV DNA (adjusted hazard ratio (aHR) = 2.6, p = 0.04) and qHBsAg nonresponse at week 4 after PD-1/PD-L1inhibitor therapy (aHR = 2.2, p = 0.04) were independent risk factors for survival.

Conclusion: PD-1/PD-L1 inhibitor therapy in patients with HBV-related HCC showed better efficacy and safety. Negative HBV DNA and a short-term decline in qHBsAg from baseline were associated with superior survival prognosis.