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.

The Role of Host in the Spectrum of Outcomes in Family Clusters of Hepatitis Infection: From Asymptomatic to Hepatocellular Carcinoma

“…One case study even displayed tumor regression after significant life stressors were relieved [14] . Other factors might include gender disparities, with studies showing worse outcomes among males [15] . The role of epigenetic mechanisms on liver tumorigenesis has also been investigated, acknowledging the importance of host interaction with the environment [16] .…”

External validation and improvement of the scoring system for predicting the prognosis in hepatocellular carcinoma after interventional therapy

“…As we all know, the male gender has been a commonly recognized risk factor for HCC recurrence (22), and increasing evidence indicates that the prognosis of HCC may be related to gender disparity, with males having worse outcomes (23). Apart from that, indicators of liver functions are also associated with HCC, as abnormalities in liver function that persist may lead to inflammation, immune microenvironment disorder, and oxidative stress.…”

Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes

“…Although several factors are decisive in the onset of HCC, such as advanced age, pro-inflammatory cytokines, the action of adipokines, smoking habits, the presence of obesity and T2D, a key role is certainly played by sexual hormones [ 83 , 84 ]. Oestrogens play a protective role against liver disease, but, as demonstrated by the epidemiological trend of liver cirrhosis and HCC, this protection is drastically reduced in women aged >65 years [ 85 ].…”

“…The clinical presentation and outcome of HCC may also differ in men and women [ 85 ]. Overall, in female patients, the progression of HCC is slower than in males, with better survival [ 85 , 86 ].…”