title: Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cattedra ed Unità Operativa di Gastroenterologia, DiBiMIS, University of Palermo, Italy. petsa@inwind.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Concetta
authors.initials: C
authors.lastname: Scazzone
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Antonino
authors.initials: A
authors.lastname: Bono
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.forename: Giusalba
authors.initials: G
authors.lastname: Licata
authors.forename: Rossana
authors.initials: R
authors.lastname: Porcasi
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxí
mesh_terms: D000328:Adult; D000368:Aged; D053493:Cholestanetriol 26-Monooxygenase / Q000032:analysis; D000072467:Cytochrome P450 Family 2; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; D012254:Ribavirin; D007372:Interferons; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase