The Impact of Hepatitis B Virus on the Tumor Microenvironment of Hepatocellular Carcinoma and Therapeutic Strategies

BACKGROUND: Hepatitis B virus (HBV) is the dominant infectious driver of hepatocellular carcinoma (HCC), but its multilevel effects on the tumor microenvironment (TME) remain incompletely catalogued, thereby constraining the advancement of future research and the refinement of clinical practice. METHODS: A comprehensive search in PubMed was conducted using the keywords "((HBV) or (Hepatitis B virus)) and ((HCC) or (hepatocellular carcinoma))". From a total of 16 473 articles, articles unrelated to tumor microenvironment or therapeutic strategies were rejected. Relevant papers published before June 2025 were included. Priority is given to authoritative articles and the latest research findings. RESULTS: The influence of HBV in the TME of HCC encompasses the generation and development of tumor cells, the number, function, and phenotype of immune cells, as well as the phenotype, characteristics, and role of other cells. Additionally, HBV is involved in reshaping the metabolic microenvironment of HCC and plays a role in the complex network within the microenvironment. The characteristics of the TME in HBV-HCC play a guiding role in the development of novel therapeutic targets, discovery of biomarkers, optimization of risk and stratification models, and improvement of clinical treatment strategies. By fully accounting for tumor heterogeneity and tailoring personalized treatment approaches for different TME subtypes, the precision and efficacy of therapies might be significantly enhanced. CONCLUSION: Deepening the understanding of the TME in HBV-HCC contributes to more precise and effective clinical treatments.