Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have reshaped the therapeutic landscape of hepatocellular carcinoma by restoring T cell-mediated antitumor immunity. However, the clinical benefit of monotherapy remains limited, highlighting the need for improved patient stratification and more effective treatment strategies. HBV-related hepatocellular carcinoma (HBV-HCC) is a major etiological subtype characterized by a chronically immunosuppressive tumor microenvironment driven by persistent viral antigen exposure and immune exhaustion. We believe that patients with HBV-HCC may be more suitable for immunotherapy, especially treatment with immune checkpoint inhibitors. A deeper understanding of the expression patterns of inhibitory checkpoint and costimulatory molecules, along with the identification of predictive biomarkers and the development of effective combination immunotherapies is essential for improving clinical outcomes. From a safety perspective, hepatitis B virus reactivation is generally manageable when appropriate antiviral therapy is administered concurrently with immunotherapy. Consequently, patients with HBV-HCC should not be excluded from treatment with immune checkpoint inhibitors. We anticipate that combination strategies, including multi-target immune checkpoint blockade, combinations with other immunotherapeutic approaches, and microbiome-based therapy, will further enhance therapeutic efficacy in HBV-HCC. Combination immune checkpoint therapy may enhance antitumor responses and potentially contribute to better control of viral activity.