Chronic inflammation and immune response in hepatocellular carcinoma: a comprehensive literature review

Chronic inflammation is an established driver of tumorigenesis across multiple organs, including the liver. Yet, the precise mechanisms linking persistent inflammatory signaling to tumorigenesis remain unclear. While classic tumor immunology focuses on immune-mediated tumor eradication, in hepatocellular carcinoma (HCC), growing evidence highlights a paradoxical immune capacity to foster malignant growth. HCC is a major health burden, most often arising in the setting of chronic inflammatory liver disease and cirrhosis. Nonetheless, some HCC cases occur in patients lacking cirrhosis or its traditional triggers, underscoring gaps in our mechanistic understanding. The immune system orchestrates a highly regulated defense network; however, neoplastic cells can subvert this network by sculpting an immune-modulating milieu that mimics protective inflammation while promoting tumor survival and expansion. In HCC, immune influences are bidirectional and stage dependent. As liver disease evolves to cirrhosis, the interplay among the inflammatory response, immune response, cirrhosis-associated immune dysfunction syndrome, and the tumor microenvironment becomes increasingly intricate. This review delineates these overlapping but distinct processes, dissects their individual contributions to HCC pathogenesis, and highlights immune-cell compositional changes across disease stages. We contrast protective immune-inflammatory responses that contain early chronic liver injury with the pro-tumorigenic environment characteristic of cirrhosis. Finally, we propose that mapping stage-specific biomarker signatures could transform inflammatory staging into a precision modality, informing immune-based prevention strategies and guiding individualized systemic therapies for HCC.