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Sex differences in hepatic encephalopathy: addressing the knowledge gap.

Lucia Lapenna1, Manuela Merli1, Marta Cilla2

  • 1Department of Translational and Precision Medicine, Sapienza University of Rome, Italy.

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|April 27, 2025
PubMed
Summary

Sex differences in hepatic encephalopathy (HE) are underexplored. This review highlights potential disparities in HE prevalence, progression, and outcomes between men and women, emphasizing the need for sex-specific research and management strategies.

Keywords:
CirrhosisGenderHepatic encephalopathySex

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Area of Science:

  • Hepatology
  • Neuroscience
  • Sex and Gender in Medicine

Background:

  • Hepatic encephalopathy (HE) is a significant complication of liver disease impacting patient quality of life and healthcare.
  • Existing research on HE predominantly overlooks potential sex-based differences in its epidemiology, clinical presentation, and underlying mechanisms.

Purpose of the Study:

  • To review and synthesize current knowledge on sex differences in hepatic encephalopathy.
  • To explore epidemiological trends, clinical manifestations, and potential biological and psychosocial mechanisms contributing to these differences.
  • To identify research gaps and advocate for sex-specific approaches in HE management.

Main Methods:

  • This narrative review was conducted by the "Gender in Hepatology" Special Interest Group (SIG) of the Italian Association for the Study of the Liver (AISF).
  • The review synthesizes existing literature on sex differences in HE, including epidemiological data, clinical observations, and emerging mechanistic insights.

Main Results:

  • Preliminary evidence suggests potential differences in HE prevalence, risk factors, and disease progression between males and females.
  • Limited research exists on sex-specific outcomes, treatment adherence, and psychological effects of HE.
  • Emerging data from body composition, gut microbiota studies, and experimental models suggest potential biological pathways underlying these sex disparities.

Conclusions:

  • Significant knowledge gaps remain regarding sex differences in hepatic encephalopathy.
  • There is a critical need for targeted research to elucidate these differences and develop sex-specific management strategies.
  • Adopting a personalized medicine approach that considers sex is essential for improving HE outcomes.