Author(s): Radwa Y Mekky 1 , Ahmed I Abdelaziz [*] 2
gender; HCV; IFN; sex hormones
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  . The fact that HCV is characterized by high mutation rates makes it capable of escaping the host immunological response  . 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)  . 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  . 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.
Viral behavior among different genders
Although HCV infection is characterized by persistence, it is documented that 15-30% of individuals show spontaneous clearance of the virus  . Gender is one of the main factors that has been widely reported to influence the HCV clearance rate, where HCV-infected females have shown higher clearance rates when compared with their male counterparts [3,4] .
The disparity in self resolution of HCV infection among males and females suggests a role for sex hormones in influencing viral behavior. However, the impact of female sex hormones on HCV remains enigmatic; it is not known whether they hold a beneficial or detrimental role towards virological clearance. For example, 17[beta]-estradiol was found to...