Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV) infection. HBV is a substantial global health problem, with close to 300 million people infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, considering how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
Highlights
Chronic infection with hepatitis B virus (HBV) is estimated to affect 257 million people[1] and accounts for an increasing burden of the 1.34 million yearly deaths due to viral hepatitis[2,3]
Sex, defined as the biological characteristics that differ between males and females[6], accounts for significant immunological differences leading to disparities in outcomes for a variety of infectious diseases[6,7], termed ‘sexual dimorphism’
Similar observations have been made in other chronic infections: in Hepatitis C virus (HCV) infection, the risk of liver disease is lower in pre-menopausal females and accelerates to match that of males when the protective effect of oestrogen exposure is lost[128]; in human immunodeficiency virus (HIV) the Toll-like receptor 7 (TLR-7) response and IFN production in women are dampened after the menopause, and restored by oestrogen replacement
Summary
Chronic infection with hepatitis B virus (HBV) is estimated to affect 257 million people[1] and accounts for an increasing burden of the 1.34 million yearly deaths due to viral hepatitis[2,3]. Similar observations have been made in other chronic infections: in HCV infection, the risk of liver disease is lower in pre-menopausal females and accelerates to match that of males when the protective effect of oestrogen exposure is lost[128]; in HIV the TLR-7 response and IFN production in women are dampened after the menopause, and restored by oestrogen replacement (reviewed in 129). Together these data confirm that oestrogen has a protective and dose-dependent effect on the course and characteristics of CHB, which may vary depending on the life history of the individual female. High rates of drug and alcohol misuse may both increase the risk of exposure to infection with blood-borne viruses, and present barriers to interaction with healthcare services, as well as being associated with vaccine hesitancy in some populations[151]
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