title: IL28B polymorphisms are associated with severity of liver disease in human immunodeficiency virus (HIV) patients coinfected with hepatitis C virus.
abstract: OBJECTIVE
  To evaluate the association of IL28B polymorphisms and severity of liver disease among human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients.
  
  
  METHODS
  We carried out a cross-sectional study on 223 patients. Liver biopsies were evaluated according to Metavir score. IL28B polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) were genotyped using GoldenGate(®) assay.
  
  
  RESULTS
  IL28B polymorphisms were in strong linkage disequilibrium, especially the couples rs12980275/rs11881222 and rs8099917/rs7248668. For all patients, the rs12980275 A allele increased the odds for significant fibrosis (F ≥ 2) odds ratio (OR) = 1.68; p = 0.018) and more rapid fibrosis progression (FPR ≥ 0.075 fibrosis units/year) (OR = 1.64; p = 0.035), and decreased the odds for liver steatosis (OR = 0.61; p = 0.046). Furthermore, the rs8099917 T allele increased the odds for F ≥ 2 (OR = 1.93; p = 0.020), FPR ≥ 0.075 (OR = 2.08; p = 0.021), and elevated ALT (≥80 IU/l) (OR = 1.78; p = 0.048). For HCV-genotype 1 patients, rs12980275 A and rs8099917 T alleles decreased the odds for liver steatosis (OR = 0.22; p < 0.001 and OR = 0.39; p = 0.048; respectively). For HCV-genotype 3 patients, the rs12980275 A allele increased the odds for F ≥ 2 ((OR = 6.30; p = 0.012), FPR ≥ 0.075 (OR = 6.40; p = 0.025), and elevated ALT (OR = 4.12; p = 0.037); and the rs8099917 T allele also increased the odds for F ≥ 2 (OR = 7.56; p = 0.027), FPR ≥ 0.075 (OR = 50.8; p = 0.012), and elevated ALT (OR = 5.39; p = 0.043). However, we did not find significant trends in patients infected with HCV-genotype 4.
  
  
  CONCLUSIONS
  The major alleles of IL28B (rs12980275 A, rs11881222 A, rs8099917 T, and rs7248668 G) are associated with increased odds of liver disease severity in HIV patients infected with HCV-genotype 3. In contrast, HCV-genotype 1 patients carrying the major alleles of IL28B polymorphisms had lower odds for liver steatosis.
authors.affiliation: Unit of HIV/Hepatitis coinfection, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez
authors.forename: Dariela
authors.initials: D
authors.lastname: Micheloud
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.forename: Pilar
authors.initials: P
authors.lastname: Miralles
authors.forename: Jaime
authors.initials: J
authors.lastname: Cosín
authors.forename: Pilar
authors.initials: P
authors.lastname: Catalán
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000483:Alleles; D060085:Coinfection; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000473:pathology*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda