Low-level HBV viremia independently predicts poor outcomes in patients with intermediate-to-advanced HBV-related hepatocellular carcinoma receiving systemic therapy: a multicenter retrospective study.

BACKGROUND

Low-level hepatitis B viremia is recognized as a potential driver of hepatocarcinogenesis; however, its prognostic impact on patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy remains poorly defined.

OBJECTIVE

To determine the independent prognostic impact of low-level viremia (LLV; HBV DNA 20-2000 IU/mL) compared with maintained virologic response (MVR; HBV DNA < 20 IU/mL) in patients with intermediate-to-advanced HBV-related HCC undergoing systemic therapy, and to evaluate whether on-treatment viral status serves as a superior predictor to baseline HBV DNA levels.

DESIGN

This was a multicenter retrospective cohort study.

METHODS

A total of 1814 patients treated at three centers between 2020 and 2024 were retrospectively enrolled. After ⩾4 months of follow-up, patients were classified into LLV (n = 860) or maintained virologic response (MVR; HBV DNA < 20 IU/mL, n = 954) groups. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. Logistic regression identified risk factors for LLV; Cox proportional hazards models assessed independent prognostic factors. Subgroup analyses were performed by treatment regimen and baseline HBV DNA load.

RESULTS

Multifactorial analysis identified HBeAg positivity (OR 1.971, 95% CI 1.53-2.541, p < 0.001), AST > 40 U/L (OR 1.437, 95% CI 1.126-1.832, p = 0.004), extrahepatic metastasis (OR 1.640, 95% CI 1.187-2.266, p = 0.003), and detectable baseline HBV DNA (OR 2.482, 95% CI 2.002-3.077, p < 0.001) as independent risk factors for LLV. Compared with the MVR group, patients in the LLV group had significantly reduced PFS (8.3 vs 14.3 months, p < 0.001) and OS (25.5 vs 37.8 months, p < 0.001). Multivariate analysis identified LLV as an independent predictor of worse OS (HR 1.506, 95% CI 1.299-1.746). Baseline HBV DNA load was not associated with survival.

CONCLUSION

LLV is a robust, independent indicator of poor prognosis in systemic-treated intermediate-to-advanced HBV-HCC and should be preferred to baseline HBV DNA load for risk stratification and to guide intensified antitumor therapy.