title: Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.
abstract: BACKGROUND
  Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH]D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR.
  
  
  METHODS
  A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH)D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All patients underwent antiviral therapy with PEG-IFN-α2a plus ribavirin. HCV RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up.
  
  
  RESULTS
  Mean ±SD 25(OH)D serum levels were 26.3 ±10.6 μg/l (range 8.0-58.0) and 31 (26.5%) patients had the rs12979860 CC polymorphism. RVR was achieved in 35 (29.9%) patients, and 32 (91.4%) of them had an SVR, compared to 26 of 82 (31.7%) without RVR. The rs12979860 CC polymorphism (OR 4.575, 95% CI 1.761, 11.889; P=0.002) and higher 25(OH)D levels (OR 1.055, 95% CI 1.010, 1.101; P=0.01) were independently associated with the achievement of RVR by multivariate analysis. The likelihood of RVR progressively increased from patients in the worst class (vitamin D<26.8 μg/l and TT/TC polymorphism; RVR 14.2%), to those with only one positive predictor (RVR 29.7% and 37.5%), and to those in the best class (vitamin D≥26.8 μg/l and rs12979860 CC polymorphism; RVR 73.3%).
  
  
  CONCLUSIONS
  In patients with G1 CHC, 25(OH)D serum levels and IL28B status are independently associated with the likelihood to achieve RVR and SVR. When incorporated into a pretreatment predictive model they can assist in further discriminating patients with a high likelihood of achieving RVR and SVR.
authors.affiliation: Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy. petsa@inwind.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Donatella
authors.initials: D
authors.lastname: Ferraro
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Stefano
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mazzola
authors.forename: Massimo
authors.initials: M
authors.lastname: Levrero
authors.forename: Concetta
authors.initials: C
authors.lastname: Scazzone
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; 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; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D059039:Standard of Care; D016896:Treatment Outcome; D019562:Viral Load; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D014807:Vitamin D; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C104450:25-hydroxyvitamin D; C100416:peginterferon alfa-2a