title: The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection.
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.
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.forename: Rachel
authors.initials: R
authors.lastname: Sacks-Davis
authors.forename: Maarten Schim
authors.initials: MS
authors.lastname: van der Loeff
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Rice
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Meghan D
authors.initials: MD
authors.lastname: Morris
authors.forename: Behzad
authors.initials: B
authors.lastname: Hajarizadeh
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Barbara H
authors.initials: BH
authors.lastname: McGovern
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.forename: Lisa
authors.initials: L
authors.lastname: Maher
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011446:Prospective Studies; D012075:Remission, Spontaneous; D012737:Sex Factors; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
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