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Semin Liver Dis
DOI: 10.1055/a-2779-4937
Review Article

Hepatic Fibrosis and Liver Cancer

Authors

  • Aina Anton

    1   Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
    2   Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States

  • Scott L. Friedman

    2   Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States
    3   Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
    4   Mount Sinai Institute for Liver Research, Icahn School of Medicine at Mount Sinai, New York, New York, United States

  • Bruno Cogliati

    2   Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States
    5   Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil

Funding Information B.C.: Grant #2022/02175-1, São Paulo Research Foundation (FAPESP).S.L.F.: NIDDK grant R01 DK128289.
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Graphical Abstract

Abstract

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.

Keywords

liver fibrogenesis - hepatocarcinogenesis - hepatic stellate cells - cancer-associated fibroblasts - tumor microenvironment


Publication History

Received: 01 October 2025

Accepted: 15 December 2025

Accepted Manuscript online:
30 December 2025

Article published online:
13 January 2026

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