HBV-positive status linked to higher surgical conversion in unresectable HCC receiving triple therapy

BackgroundThe combination of transarterial chemoembolization (TACE), lenvatinib, and PD-1 inhibitors has shown promising efficacy in treating advanced hepatocellular carcinoma (HCC). However, the impact of hepatitis B virus (HBV) infection on the outcomes of this therapy remains unclear. This study aims to assess the association between HBV infection status and clinical outcomes in patients with initially unresectable HCC undergoing triple therapy.MethodsThis retrospective single-center cohort study included 190 consecutive uHCC patients treated with triple therapy between February 2022 and February 2025. Patients were stratified into HBV-positive (n = 133) and HBV-negative (n = 57) groups based on HBsAg status. Propensity score matching (PSM, 1:1, caliper 0.02) was performed to balance baseline characteristics. The primary endpoint was surgical conversion. Secondary endpoints included tumor response (mRECIST), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Landmark analyses, subgroup analyses and multivariate Cox regression were used to evaluate clinical outcomes and independent prognostic factors.ResultsCompared to HBV-negative patients, HBV-positive patients achieved significantly higher surgical conversion rates both before PSM (25.6% vs. 12.3%, P = 0.041) and after PSM (20% vs. 10%, P = 0.021). After PSM, 30 matched pairs were included. Median OS was not reached in the HBV-positive patients and was 20.0 months in the HBV-negative patients (95% CI, 17.1–22.9; P = 0.014). Median PFS was 28.4 months (95% CI, 25.6–31.2) versus 17.3 months (95% CI, 14.8–19.9; P = 0.030). Tumor response was superior in the HBV-positive group, with higher ORR (36.7% vs. 20%, P = 0.043) and DCR (83.3% vs. 60%, P = 0.045). HBV-positive patients exhibited significantly prolonged OS (P = 0.014) and PFS (P = 0.030). Landmark analysis showed that the PFS advantage in HBV-positive patients no longer statistically significant (P = 0.118). Tumor diameter and HBV infection status were independent predictor of OS and PFS. Grade 3–4 AEs were comparable between groups, and no treatment-related deaths occurred.ConclusionsHBV-positive status was associated with higher conversion rates and more favorable survival outcomes in unresectable HCC treated with TACE, lenvatinib, and PD-1 inhibitors. Prospective validation is needed to confirm these findings and clarify their biological basis.