title: Responder Interferon λ Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.
abstract: Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon λ3 (IFN-λ3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-λ genotypes and significant liver fibrosis in HIV-HCV coinfection.
  
  
  
  From the prospective Canadian Co-infection Cohort (n = 1423), HCV RNA-positive participants in whom IFN-λ genotypes were detected and who were free of fibrosis, end-stage liver disease, and chronic hepatitis B at baseline (n = 485) were included. Time to significant fibrosis (defined as an aspartate transaminase level to platelet count ratio index [APRI] of ≥1.5) by IFN-λ genotypes was analyzed using Cox proportional hazards, with adjustment for age, sex, ethnicity, alcohol use, CD4(+) T-cell count, HCV genotype, γ-glutamyl transferase level, and baseline APRI. Haplotype analysis was performed, with adjustment for ethnicity.
  
  
  
  A total of 125 participants developed fibrosis over 1595 person-years (7.84 cases/100 person-years; 95% confidence interval [CI], 6.58-9.34 cases/100 person-years). Each genotype was associated with an increased fibrosis risk, with adjusted hazard ratios of 1.37 (95% CI, .94-2.02) for rs12979860CC, 1.34 (95% CI, .91-1.97) for rs8103142TT, and 1.79 (95% CI, 1.24-2.57) for rs8099917TT. Haplotype TCT was also linked with a higher risk (hazard ratio, 1.14 [95% CI, .73-1.77]).
  
  
  
  IFN-λ SNPs rs12979860, rs8099917, and rs81013142 were individually linked to higher rates of fibrosis in individuals with HIV-HCV coinfection. IFN-λ genotypes may be useful to target HCV treatments to people who are at higher risk of liver disease.
authors.affiliation: Epidemiology, Biostatistics, Occupational Health, McGill University.
authors.forename: Nasheed
authors.initials: N
authors.lastname: Moqueet
authors.affiliation: Ottawa Hospital-Research Institute.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Southern Alberta HIV Clinic, Calgary.
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Hull
authors.affiliation: Epidemiology, Biostatistics, Occupational Health, McGill University.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Epidemiology, Biostatistics, Occupational Health, McGill University Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002170:Canada; D015331:Cohort Studies; D060085:Coinfection / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000235:genetics* / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons
keywords: HIV-HCV co-infection; IFNL; liver fibrosis