Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Abstract

Infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC) in developed countries. Epidemiological reports indicate that the incidence of HBV-related HCC is higher in males and postmenopausal females than other females. Increasing evidence suggests that sex hormones such as androgens and estrogens play an important role in the progression of an HBV infection and in the development of HBV-related HCC. While androgen is supposed to stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes, estrogen may play a protecting role against the progression of HBV infections and in the development of HBV-related HCC through decreasing HBV RNA transcription and inflammatory cytokines levels. Additionally, sex hormones can also affect HBV-related hepatocarcinogenesis by inducing epigenetic changes such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation, and histone modification in liver tissue. This review describes the molecular mechanisms underlying the gender disparity in HBV-related HCC with the aim of improving the understanding of key factors underneath the sex disparity often observed in HBV infections. Furthermore, the review will propose more effective prevention strategies and treatments of HBV-derived diseases.

Dose‐response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

“…Of note, it is an interesting but unsolved issue whether those carriers with the lowest detectable serum titer of HBsAg, say 0.05 to 9 IU/ml, have the identical or higher risk of liver cancer compared with the HBsAg‐negative subjects. Besides, increasing evidence indicates that HBV‐related HCC may involve gender disparity and that it may be a type of hormone‐responsive malignant tumor . One remarkable clinical feature of HBV‐related HCC is that its incidence is higher in males compared to females .…”

Pre‐diagnostic urinary 15‐F2t‐isoprostane level and liver cancer risk: Results from the Shanghai Women's and Men's Health Studies

“…A notable gender disparity was observed on the dose–response association between 15‐F 2t ‐IsoP level and liver cancer risk in our study. Increasing evidence suggested that sex hormones such as androgens and estrogens played an important role in the development of liver cancer and regulating the level of oxidative stress . It was supposed that androgen may stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes .…”

“…Increasing evidence suggested that sex hormones such as androgens and estrogens played an important role in the development of liver cancer and regulating the level of oxidative stress . It was supposed that androgen may stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes . In contrast, estrogen may play a protecting role against the development of liver cancer through decreasing HBV RNA transcription and inflammatory cytokines levels .…”

Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers

“…Liver cancers are discovered through the use of medical imaging equipment (often by accident) or present themselves symptomatically as an abdominal mass, abdominal pain, yellow skin, nausea or liver dysfunction [62,63] . The leading cause of liver cancer is cirrhosis that occurs due to infection caused by hepatitis B or hepatitis C, or due to excess consumption of alcohol [64] . In fact, in 2013, 300,000 deaths from liver cancer were due to hepatitis B, 343,000 due to hepatitis C and 92,000 due to heavy alcohol intake [64,65] .…”

“…The leading cause of liver cancer is cirrhosis that occurs due to infection caused by hepatitis B or hepatitis C, or due to excess consumption of alcohol [64] . In fact, in 2013, 300,000 deaths from liver cancer were due to hepatitis B, 343,000 due to hepatitis C and 92,000 due to heavy alcohol intake [64,65] . Also, liver is one of the most common sites for metastatic disease, and optimal management of hepatic metastases often requires a multidisciplinary approach [66] .…”