title: Vitamin A deficiency is associated with hepatitis C virus chronic infection and with unresponsiveness to interferon-based antiviral therapy.
abstract: Recent data suggest that vitamin A modulates the expression of type I interferon receptor enhancing the antireplication effect of interferon-α on hepatitis C virus (HCV). This study aimed to investigate the prevalence of vitamin A deficiency among patients with chronic HCV infection and to assess whether vitamin A deficiency could be associated with unresponsiveness to interferon-based antiviral therapy. The analysis included 199 consecutive treatment-naïve chronic HCV patients in whom pretreatment serum vitamin A and 25-OH vitamin D were measured; 119 healthy blood donors were used as controls. Median (interquartile range) serum vitamin A in HCV-positive patients was significantly lower than in controls: 256 ng/mL (128-440) versus 742 (624-942, P<0.0001). Overall sustained viral response was achieved in 122/199 patients, 46/109 infected by difficult to treat HCV genotypes. In these latter, 39/104 (37.5%) were nonresponders. At multivariate analysis, nonresponse to antiviral therapy was predicted by carriage of interleukin (IL)-28B T/* genotypes, baseline serum levels of γGT>60 IU/mL, of HCV RNA>600,000 IU/mL, of vitamin A≤100 ng/mL, and a cumulative dose of ribavirin≤80%. Seventeen patients (9.0%) had both serum levels of vitamin A≤100 ng/mL and of vitamin D≤20 ng/mL; the presence of a combined vitamin A and D deficiency was found to be a strong independent predictor of nonresponse to antiviral therapy.
  
  
  CONCLUSIONS
  A high percentage of patients with chronic HCV infection have serum vitamin A deficiency. This condition is associated with nonresponse to antiviral therapy.
authors.affiliation: Department of Medical Sciences Experimental and Clinical, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Nadia
authors.initials: N
authors.lastname: Bortolotti
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Sara
authors.initials: S
authors.lastname: Vescovo
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fattovich
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Ezio
authors.initials: E
authors.lastname: Fornasiere
authors.forename: Elisa
authors.initials: E
authors.lastname: Ceriani
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000097:blood / Q000453:epidemiology*; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000453:epidemiology; D014815:Vitamins / Q000097:blood; 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; D014801:Vitamin A; D014807:Vitamin D; D014815:Vitamins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b