August 11, 2013

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


Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Viral Hepatitis

Jason Grebely1,*, Kimberly Page2, Rachel Sacks-Davis3,4, Maarten Schim van der Loeff5,6, Thomas M. Rice2, Julie Bruneau7, Meghan D. Morris2, Behzad Hajarizadeh1, Janaki Amin1, Andrea L. Cox8, Arthur Y. Kim9, Barbara H. McGovern10,11, Janke Schinkel12, Jacob George13, Naglaa H. Shoukry7, Georg M. Lauer9, Lisa Maher1, Andrew R. Lloyd14, Margaret Hellard3,4, Gregory J. Dore1, Maria Prins5,6, the InC3 Study Group

DOI: 10.1002/hep.26639

© 2013 by the American Association for the Study of Liver Diseases

Publication History

Accepted manuscript online: 2 AUG 2013 05:29AM EST, Manuscript Accepted: 16 JUL 2013, Manuscript Revised: 23 MAY 2013, Manuscript Received: 19 APR 2013


Keywords: injection drug use; hepatitis C virus; HIV; incident infection; longitudinal studies

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's 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 5% 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 2013;)


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