Combining Antiviral Therapy with Cancer Treatment in HBV-associated HCC: A Translational Approach

Hepatitis B virus (HBV) infection remains a major global health concern and is a leading cause of hepatocellular carcinoma (HCC). Despite advances in antiviral therapy and cancer treatment, HBV-related HCC (HBV-HCC) continues to pose significant challenges due to its complex pathogenesis involving chronic inflammation, viral persistence, and liver fibrosis. Current antiviral therapies reduce viral load and liver inflammation but often fail to eliminate integrated viral DNA or prevent carcinogenesis. On the other hand, cancer therapies such as surgery, ablation, immunotherapy, and targeted therapy have limited success when used in isolation, especially in patients with active HBV replication. This review examines the emerging concept of combining antiviral and anticancer strategies to improve clinical outcomes in HBV-HCC. We discuss the molecular mechanisms linking HBV infection to HCC, the role of antiviral therapy in reducing recurrence post-HCC treatment, and the impact of HBV reactivation during cancer therapy. In addition, we explore emerging biomarkers for early detection and prognosis, the therapeutic implications of HBV DNA integration, and the potential of gene-editing technologies targeting viral reservoirs. We further review the influence of HBV-induced immune dysregulation on immunotherapy outcomes, the relevance of host-microbiome interactions in liver carcinogenesis, and the utility of precision medicine approaches in guiding treatment. We highlight recent translational studies, clinical trials, and future directions that support a dual-modality approach, aiming for long-term remission and improved survival in patients with HBV-HCC.