Hepatic Fibrosis and Liver Cancer

Primary liver cancer, or hepatocellular carcinoma (HCC), typically emerges in fibrotic livers where persistent inflammation and extracellular matrix (ECM) remodeling create a permissive niche for malignant transformation. Although cirrhosis remains a major risk factor, mounting data show that fibrosis itself, often in the context of metabolic dysfunction-associated steatotic liver disease (MASLD), can promote hepatocarcinogenesis even before cirrhosis develops. This review synthesizes mechanistic insights from hepatic stellate cell (HSC) biology and tumor immunology that position fibrosis as an instigator of HCC. Fibrotic remodeling increases ECM stiffness, distorts sinusoidal architecture, and promotes abnormal angiogenesis, while HSCs reprogram immune surveillance toward immune cell exclusion and immunosuppression. Aging and cellular senescence amplify these effects through a senescence-associated secretory phenotype in HSCs and hepatocytes, which fuels chronic inflammation and immune dysfunction. Metabolic crosstalk and extracellular vesicle exchange further couple stromal and epithelial programs, reinforcing stemness, therapy resistance, and metastatic fitness. In conclusion, the convergence of fibrogenic and oncogenic signaling drives HCC, uncovering actionable targets for its prevention and treatment.