Gender Disparity in Host Responses to Hepatitis B-Related Hepatocellular Carcinoma: A Case Series

Abstract

Chronic hepatitis B virus (HBV) infection is one of the most common causes of hepatocellular carcinoma (HCC), a malignant tumor with high mortality worldwide. One remarkable clinical feature of HBV-related HCC is that the risk of development is higher in males and postmenopausal females compared to other females. Increasing evidence also indicates that the prognosis of HBV-associated HCC may involve gender disparity, with females having more favorable outcomes. The proposed mechanism of this gender disparity is thought to be complex and multifactorial. Attributions have been made to gender differences in behavioral risk factors, host stress, immune response, psychology, metabolic risk factors, tumor biology, and hormonal factors. Gender disparities in hormonal factors and stress with consequent incited inflammation and hepatocarcinogenesis in HBV-related HCC is a particularly burgeoning area of investigation. Clarifying these mechanisms could provide insight into HBV-related HCC pathogenesis, and potentially provide a target for prevention and treatment of this disease. Reported herein is a case series involving two families affected by vertically transmitted chronic hepatitis B, longitudinally observed over multiple decades, with family members demonstrating discordant outcomes related to HCC, with worse outcomes among affected males. As a supplement to this case, we review the currently available literature on gender differences in outcomes from HBV-related HCC. In reporting this case series, we aim to add our important observation to the current literature and highlight the need for further research in the mechanisms involved in gender disparity in the prognosis of HBV-related HCC.

Keywords: androgens; chronic hepatitis B; estrogens; gender disparity; hepatitis B virus; hepatocellular carcinoma; prognosis; sex difference; stress; survival.

Figure 1

Pedigree of one family cluster (family 1) depicting the current clinical status of family members as of May 2021. Abbreviations: chronic hepatitis B (CHB), hepatocellular carcinoma (HCC), years old (y.o.).

Figure 2

Pedigree of one family cluster (family 2) depicting the current clinical status of family members as of May 2021. Abbreviations: HBV (hepatitis B virus), chronic hepatitis B (CHB), hepatocellular carcinoma (HCC), years old (y.o.).