Sex Hormones and HCV

An Unresolved Mystery

Radwa Y Mekky; Ahmed I Abdelaziz

Disclosures

Expert Rev Gastroenterol Hepatol. 2013;7(1):69-75. 

In This Article

Abstract and Introduction

Abstract

The biological differences between males and females advocate the ultimate need for gender-specific medicine. The variation in response to viral infection as well as therapy among different genders makes it very intriguing to reveal the responsible factors for causing this discrepancy. HCV is one of the most noxious infectious diseases, however the impact of gender on the response to HCV has received negligible attention in the literature. The controversial studies concerning the effect of gender on the outcome of interferon-based therapy urge a need to judge the gender discrepancy in host factors responsible for both interferon release and action. The main aim of this review is to disentangle the interplay between sex hormones and several viral and host factors responsible for viral clearance in an attempt to clarify the role of gender in modulating the response to HCV as well as interferon-based therapy.

Introduction

The numerous diversities among males and females make them respond variably to disease and therapy. This variation has stimulated an interest in the implementation of gender-specific medicine, wherein the genetic diversity between different genders is taken into consideration. Accordingly, the therapeutic dosage given to either males or females is adjusted in an attempt to reach the optimal therapeutic outcome with minimal adverse events.

Chronic hepatitis C infection is considered a major healthcare burden worldwide, with high prevalence in Africa and the Middle East, especially in Egypt.[1] The fact that HCV is characterized by high mutation rates makes it capable of escaping the host immunological response.[2] Consequently most HCV-infected patients suffer a chronic form of infection. Recently gender has emerged as a major factor affecting the innate response to HCV; the rate of spontaneous clearance of HCV was found to be higher among HCV-infected females when compared with male patients.[3–5] The exact factors responsible for this variability in the natural history of the disease are still not well known.

Gender has also been suspected to contribute to the variable response to standard HCV therapy (pegylated interferon (IFN) and ribavirin).[6] The goal of standard therapy of HCV infection is to achieve a sustained virologic response (SVR), which is defined as the absence of HCV RNA in the serum, 6 months after the end of treatment.[7] Unfortunately, the possible effects of gender on treatment response are still contested. On one hand, some recent studies have revealed that an SVR is more prominent among male patients.[8,9] On the other hand, female gender has been widely reported to be a good prognostic factor to IFN based therapy.[10–12] Alternatively, various studies have denied the association between gender and the outcome of therapy.[13–16] To help unravel the ambiguity surrounding this issue an important question should be investigated: could the actions of sex hormones on viral and host factors explain the disparate rates of viral clearance and response to therapy between males and females? Thus this review aims at analyzing the sex hormones' impact on viral and host factors that are important in viral clearance in an attempt to demystify the gender variation in self-limited infection to HCV and therapeutic response to IFN-based therapy.

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