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Multicenter Study
. 2014 Jan;59(1):109-20.
doi: 10.1002/hep.26639. Epub 2013 Nov 22.

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

Jason Grebely  1 , Kimberly Page, Rachel Sacks-Davis, Maarten Schim van der Loeff, Thomas M Rice, Julie Bruneau, Meghan D Morris, Behzad Hajarizadeh, Janaki Amin, Andrea L Cox, Arthur Y Kim, Barbara H McGovern, Janke Schinkel, Jacob George, Naglaa H Shoukry, Georg M Lauer, Lisa Maher, Andrew R Lloyd, Margaret Hellard, Gregory J Dore, Maria Prins; InC3 Study Group
Collaborators, Affiliations
Multicenter Study

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

Jason Grebely et al. Hepatology. 2014 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1
Kaplan-Meier graphs of time to spontaneous clearance in A) the overall population with acute HCV infection (n=632) and B) those with early acute HCV infection (n=183). 95% confidence intervals are in shaded grey.
Figure 2
Figure 2
Kaplan-Meier graphs of time to viral clearance by A) Age; B) Sex; C) Symptomatic HCV infection; D) IL28B genotype; and E) HCV genotype.
Figure 3
Figure 3
Predictors of time to spontaneous HCV clearance among participants with acute HCV infection.
Figure 4
Figure 4
Kaplan-Meier graphs of time to viral clearance by A) Sex and IL28B genotype; B) Sex and HCV genotype; and C) IL28B genotype and HCV genotype.
See this image and copyright information in PMC

Comment in

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