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World J Gastroenterol. May 28, 2014; 20(20): 6252-6261
Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.6252
Molecular mechanisms of gender disparity in hepatitis B virus-associated hepatocellular carcinoma
Wei-Cheng Liu, Quan-Yan Liu
Wei-Cheng Liu, Quan-Yan Liu, Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430030, Hubei Province, China
Author contributions: Liu QY contributed to the conception, design of the article and manuscript editing; Liu WC carried out the literature review in addition to the completion of the initial manuscript; all authors were involved in revising the manuscript critically for important intellectual content.
Supported by National Natural Science Foundation of China, Nos. 81372552 and 81172349/H1617
Correspondence to: Quan-Yan Liu, MD, PhD, Professor, Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuhan 430071, Hubei Province, China. lqy@whu.edu.cn
Telephone: +86-27-87330795 Fax: +86-27-87330795
Received: October 13, 2013
Revised: December 22, 2013
Accepted: January 8, 2014
Published online: May 28, 2014
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 its incidence is higher in males and postmenopausal females compared to other females. Increasing evidence indicates that HBV-associated HCC may involve gender disparity and that it may be a type of hormone-responsive malignant tumor. Sex hormones, such as androgen and estrogen, have been shown to play very different roles in the progression of an HBV infection and in the development of HBV-related HCC. Through binding to their specific cellular receptors and affecting the corresponding signaling pathways, sex hormones can regulate the transactivation of HBx, cause the chronic release of inflammatory cytokines in the hepatocellular microenvironment, and participate in epigenetic and genetic alternations in hepatocytes. All of these functions may be related to the initiation and progression of HBV-associated HCC. A thorough investigation of the molecular mechanisms underlying the gender-related disparity in HBV-related HCC should provide a new perspective for better understanding its pathogenesis and exploring more effective methods for the prevention and treatment of this disease.

Keywords: Hepatitis B virus, Hepatocellular carcinoma, Gender disparity, Sex hormones

Core tip: Increasing evidence indicates that hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) may involve gender disparity and that it may be a type of hormone-responsive malignant tumor. Sex hormones have been shown to play very different roles in the progression of an HBV infection and in the development of HBV-related HCC. The article reviews the reported molecular mechanisms of the gender disparity in HBV-related HCC, with an aim to improve the understanding of the development and progression of HBV-associated HCC and exploring more effective prevention and treatment of this disease.