Vitamin A deficiency is associated with hepatitis C virus chronic infection and with unresponsiveness to interferon-based antiviral therapy

Hepatology. 2013 Mar;57(3):925-33. doi: 10.1002/hep.26186. Epub 2013 Feb 7.


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.

Conclusion: A high percentage of patients with chronic HCV infection have serum vitamin A deficiency. This condition is associated with nonresponse to antiviral therapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / epidemiology*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • Vitamin A / blood
  • Vitamin A Deficiency / blood
  • Vitamin A Deficiency / epidemiology*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology
  • Vitamins / blood


  • Antiviral Agents
  • IFNL3 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Vitamins
  • Vitamin A
  • Vitamin D
  • Polyethylene Glycols
  • Interferons
  • peginterferon alfa-2b