title: Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C.
abstract: The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or ≤20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels >20 ng/mL (group C) or ≤20 ng/mL (group D)-a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) (P < 0.0001).
  
  
  CONCLUSIONS
  Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C.
authors.affiliation: Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fattovich
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Elisa
authors.initials: E
authors.lastname: Ceriani
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Ezio
authors.initials: E
authors.lastname: Fornasiere
authors.forename: Michela
authors.initials: M
authors.lastname: Pasino
authors.forename: Donatella
authors.initials: D
authors.lastname: Ieluzzi
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; 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; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014807:Vitamin D; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C104450:25-hydroxyvitamin D; C417083:peginterferon alfa-2b