title: IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C.
abstract: BACKGROUND
  Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue.
  
  
  OBJECTIVE
  To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC).
  
  
  METHODS
  Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study.
  
  
  RESULTS
  Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR=0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age <40 years (OR=4.79; 1.50-15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR=6.26; 1.98-19.74) and age <40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67).
  
  
  CONCLUSIONS
  In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.
authors: Clinic of Gastroenterology, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, Verona, Italy. giovanna.fattovich@univr.it
authors: G
authors: G
authors: Fattovich
authors: L
authors: L
authors: Covolo
authors: S
authors: S
authors: Bibert
authors: G
authors: G
authors: Askarieh
authors: M
authors: M
authors: Lagging
authors: S
authors: S
authors: Clément
authors: G
authors: G
authors: Malerba
authors: M
authors: M
authors: Pasino
authors: M
authors: M
authors: Guido
authors: M
authors: M
authors: Puoti
authors: G B
authors: GB
authors: Gaeta
authors: T
authors: T
authors: Santantonio
authors: G
authors: G
authors: Raimondo
authors: R
authors: R
authors: Bruno
authors: P-Y
authors: PY
authors: Bochud
authors: F
authors: F
authors: Donato
authors: F
authors: F
authors: Negro
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000097:blood*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D054357:Chemokine CXCL10; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a