Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C

Hepatology. 2010 Apr;51(4):1158-67. doi: 10.1002/hep.23489.


25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were assessed by immunochemistry in 34 patients with CHC, and in eight controls. The 25(OH)D serum levels were significantly lower in CHC than in controls (25.07 +/- 9.92 microg/L versus 43.06 +/- 10.19; P < 0.001). Lower levels of 25(OH)D were independently linked to female sex (P = 0.007) and necroinflammation (P = 0.04) by linear regression analysis. CYP27A1, but not CYP2R1, was directly related to 25(OH)D levels (P = 0.01), and inversely to necroinflammation (P = 0.01). Low 25(OH)D (odds ratio [OR], 0.942; 95% confidence interval [CI], 0.893-0.994) and cholesterol (OR, 0.981; 95%CI, 0.969-0.992) levels, older age (OR, 1.043; 95%CI, 1.002-1.085), high ferritin (OR, 1.003; 95%CI, 1.001-1.005), and necroinflammation (OR, 2.235; 95%CI, 1.014-4.929) were independently associated with severe fibrosis (F3-F4) by multivariate logistic analysis. Seventy patients (41%) achieved SVR. By multivariate analysis, hepatic steatosis (OR, 0.971; 95%CI, 0.944-0.999), lower cholesterol (OR, 1.009; 95% CI, 1.000-1.018), and 25(OH)D levels (OR, 1.039; 95%CI, 1.002-1.077) were independently associated with no SVR.

Conclusion: G1 CHC patients had low 25(OH)D serum levels, possibly because of reduced CYP27A1 expression. Low vitamin D is linked to severe fibrosis and low SVR on interferon (IFN)-based therapy.

MeSH terms

  • Adult
  • Aged
  • Cholestanetriol 26-Monooxygenase / analysis
  • Cytochrome P450 Family 2
  • Female
  • Genotype
  • Hepacivirus / classification
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons / therapeutic use*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / etiology*
  • Male
  • Middle Aged
  • Ribavirin / administration & dosage
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Vitamin D
  • Ribavirin
  • Interferons
  • 25-hydroxyvitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase