The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection


  • Potential conflict of interest: Dr. Bruneau received grants from Merck. Dr. Dore consults, advises, is on the speakers' bureau, and received grants from Merck and Janssen. He advises, is on the speakers' bureau, and received grants from Roche. Dr. Grebely advises and received grants from Merck. He owns stock in Gilead.

  • The InC3 Study is supported by the National Institute on Drug Abuse (NIDA; award no.: R01DA031056). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDA or the National Institutes of Health (NIH). The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this article do not necessarily represent the position of the Australian Government. J.Gr. is supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship. J.B. and N.H.S. are supported by Fonds de la Recherche du Québec-Santé Research Career Awards. B.H. is supported by an Australian Postgraduate Ph.D. Award. G.D. and A.L. are supported by NHMRC Practitioner Research Fellowships. M.H. and L.M. were supported by NHMRC Senior Research Fellowships and M.H. additionally by a VicHealth Senior Research Fellowship. R.S.D. was supported by an NHMRC postgraduate scholarship and a Centre for Research Excellence into Injecting Drug Use postgraduate top-up scholarship. Other research support includes NIH U19 AI088791 (to A.C.), NIH U19 AI066345 (to A.Y.K., G.M.L., and B.H.M.), U19 AI082630 (the National Institute of Allergy and Infectious Diseases; to G.M.L.), R01 DA033541 (NIDA; to A.Y.K.), MOP-103138 and MOP-210232 (the Canadian Institutes of Health Research; to J.B. and N.H.S.), and the Netherlands National Institute for Public Health and the Environment (to M.Svd.L. and M.P.). J.Ge. is supported by the Sydney Medical Foundation and grants from the NHMRC.


Although 20%-40% of persons with acute hepatitis C virus (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 after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin-28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. 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 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 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 (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus 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. (Hepatology 2014;58:109–120)