Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients

Abstract

Lower 25-hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023-1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974-0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002-1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919-0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106-16.120; P = 0.03), moderate-severe steatosis (OR, 2.588; 95% CI, 1.355-4.943; P = 0.004) and moderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307-4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.

Association between serum vitamin D and severity of liver fibrosis in chronic hepatitis C patients: a systematic meta-analysis

“…A lower serum 25(OH) D level significantly correlates with an increasing risk of advanced fibrosis and a higher severity of necroinflammatory activity has been related to different populations with individuals infected with chronic hepatitis C (Lange et al, 2011;Kitson et al, 2013;Petta et al, 2013). However, the results are not consistent in different studies and by race (Kitson et al, 2013;White et al, 2013).…”

“…Our total search yielded 775 entries. We identified six eligible publications (Arteh et al, 2010;Lange et al, 2011;Amanzada et al, 2013;Kitson et al, 2013;Petta et al, 2013;White et al, 2013) concerning the association between vitamin D and severity of liver fibrosis in patients infected with chronic hepatitis C. Among these studies, two (Arteh et al, 2010;Petta et al, 2013) were consecutive studies, one (Lange et al, 2011) was a retrospective study, one (White et al, 2013) was a cross-sectional study, one (Kitson et al, 2013) was a CHARIOT study, and one was a cohort study (Amanzada et al, 2013).…”

“…Of these six studies, three (Lange et al, 2011;Amanzada et al, 2013;Petta et al, 2013) were conducted in Europe, two (Arteh et al, 2010;White et al, 2013) …”

“…n c : number of cases; n p : number of participants; M: male; F: female; CHARIOT: collaborative group hepatitis C study using high-dose Pegasys RBV induction dose in genotype one; HPLC: high performance liquid chromatography; LC: liquid chromatography; MS: mass spectrometry; G1, 2, 3, 4: hepatitis C genotype 1, 2, 3, or 4 infection; NA: not available United States, and one (Kitson et al, 2013) in Australia. The five (Arteh et al, 2010;Amanzada et al, 2013;Kitson et al, 2013;Petta et al, 2013;White et al, 2013) studies assessed included a review of serum 25(OH) D status, and one (Lange et al, 2011) on 25(OH)D 3 and 1,25(OH) 2 D 3 status. Three studies (Amanzada et al, 2013;Kitson et al, 2013;Petta et al, 2013) included patients with chronic hepatitis C genotype 1 infection, one (Lange et al, 2011) with chronic hepatitis C genotype 1, 2, or 3-infection, one (White et al, 2013) with chronic hepatitis C genotype 1, 2, 3, or 4-infection, and one (Arteh et al, 2010) did not specify the kind of HCV type.…”

“…The five (Arteh et al, 2010;Amanzada et al, 2013;Kitson et al, 2013;Petta et al, 2013;White et al, 2013) studies assessed included a review of serum 25(OH) D status, and one (Lange et al, 2011) on 25(OH)D 3 and 1,25(OH) 2 D 3 status. Three studies (Amanzada et al, 2013;Kitson et al, 2013;Petta et al, 2013) included patients with chronic hepatitis C genotype 1 infection, one (Lange et al, 2011) with chronic hepatitis C genotype 1, 2, or 3-infection, one (White et al, 2013) with chronic hepatitis C genotype 1, 2, 3, or 4-infection, and one (Arteh et al, 2010) did not specify the kind of HCV type. Four studies (Baur et al, 2012;Corey et al, 2012;Weintraub et al, 2012;Ladero et al, 2013) were excluded because they did not report usable data.…”