Riccardo Nevola, Giovanni Tortorella, Valerio Rosato, Luca Rinaldi, Simona Imbriani, Pasquale Perillo, Davide Mastrocinque, Marco La Montagna, Antonio Russo, Giovanni Di Lorenzo, Maria Alfano, Maria Rocco, Carmen Ricozzi, Klodian Gjeloshi, Ferdinando Carlo Sasso, Raffaele Marfella, Aldo Marrone, Loreta Anesti Kondili, Nicolino Esposito, Ernesto Claar, Domenico Cozzolino

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

  • General Agricultural and Biological Sciences
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
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Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.

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