title: Association of IL28B genotype with fibrosis progression and clinical outcomes in patients with chronic hepatitis C: a longitudinal analysis.
abstract: Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinical outcome is unclear. Our aim was to study the relationship between IL28B genotype and both histological and clinical outcomes in patients with chronic hepatitis C (CHC). Hepatic fibrosis was scored using the Ishak (0-6) scale; progression was defined as a 2-point increase in Ishak score between biopsies. Multiple logistic and Cox regressions were used to identify variables associated with fibrosis progression. In all, 1,483 patients were included in a baseline cross-sectional analysis, from which 276 were eligible for a paired biopsy analysis (median time between biopsies 4 years), and 400 for a clinical outcome analysis. At baseline biopsy, patients with IL28B CC genotype had significantly higher portal inflammation (2.4 versus 2.2) and alanine aminotransferase (ALT) levels (133 versus 105 U/L; P < 0.05 for all). In the paired biopsy analysis, there was no difference in the frequency of fibrosis progression between patients with IL28B CC and non-CC genotypes (17% versus 23%). In logistic regression, only higher baseline alkaline phosphatase, lower platelets, and greater hepatic steatosis were associated with fibrosis progression. Patients with IL28B CC were twice as likely to develop adverse clinical outcomes compared to non-CC (32% versus 16%; P = 0.007).
  
  
  CONCLUSIONS
  IL28B CC genotype was associated with greater hepatic necroinflammation, higher ALT, and worse clinical outcomes in CHC patients. This suggests that IL28B CC is associated with a state of enhanced immunity that, on the one hand, can promote viral clearance, but alternately can increase necroinflammation and hepatic decompensation without enhancing fibrosis progression.
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Mazen
authors.initials: M
authors.lastname: Noureddin
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: Shauna
authors.initials: S
authors.lastname: Clark
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Thomas
authors.forename: Richard
authors.initials: R
authors.lastname: Chen
authors.forename: Xiongce
authors.initials: X
authors.lastname: Zhao
authors.forename: Cathy
authors.initials: C
authors.lastname: Conry-Cantilena
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda