The effects of female sex, viral genotype, andIL28Bgenotype on spontaneous clearance of acute hepatitis C virus infection

Abstract

Although 20–40% of persons with acute HCV infection demonstrate spontaneous clearance, the time-course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes following acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had IL28B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1 and 5% had HIV co-infection. Twenty-eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow-up, spontaneous clearance occurred in 173 of 632 and at one year following infection, 25% (95%CI: 21%, 29%) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4 weeks), with 34%, 67% and 83% demonstrating clearance at three, six and twelve months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex [adjusted hazards ratio (AHR) 2.16; 95%CI 1.48, 3.18], IL28B CC genotype (vs. CT/TT, AHR 2.26; 95%CI 1.52, 3.34), and HCV genotype 1 (vs. non-genotype 1, AHR 1.56; 95%CI 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females compared to males. Conclusions Female sex, favorable IL28B genotype and HCV genotype 1 are independent predictors of spontaneous clearance. Further research is required to elucidate the observed sex-based differences in HCV control.

Hepatitis C virus infection in the general population: A large community-based study in Mianyang, West China

“…The underlying reason of male predominance in this study is still not clear. However, studies have demonstrated that, on average, about 20% of HCV infected individuals would spontaneously clear the virus after initial infection, and women were more likely to clear the virus spontaneously (23,24). In addition, we hypothesized that there may be more chances for men to be infected by HCV through unhealthy lifestyles or behaviors, such as smoking, drinking, poor hygiene, and unhealthy sexual activities.…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Finally, the statistical methods and definitions used to determine clearance estimates vary among studies. Of those who are able to spontaneously clear HCV, most do so within 12 weeks of seroconversion, although spontaneous clearance after a longer period of follow-up has also been described [12]. The HCV RNA clearance rate is higher when clearance is defined as a single negative HCV RNA result compared with two negative HCV RNA results, which should be the preferred definition of RNA clearance [13].…”

Natural Killer Cells in HCV Infection

“…It is demonstrated that spontaneous clearance of HCV occurs most often after the induction of an anti-HCV humoral immune response [42,43], indicating that antibodymediated immune responses, such as NK-ADCC, may contribute to the spontaneous clearance of HCV. Jacob et al demonstrate that specific antibodies to HCV E2 in serum can mediate ADCC activity, while the pathological mechanisms have not yet been studied in chronic HCV infection [44].…”