Vitamin D supplementation improves serum markers associated with hepatic fibrogenesis in chronic hepatitis C patients: A randomized, double-blind, placebo-controlled study

Abstract

Hepatic fibrosis is the net accumulation of matrix tissue components which controlled by pro-fibrolytic enzymes, matrix metalloproteinases (MMPs), and pro-fibrotic cytokine, TGF-β₁, and enzymes, tissue inhibitors of MMPs (TIMPs). Vitamin D (VD) supplementation has been shown to reverse these processes in vitro and in vivo. This study sought to determine the effect of VD supplementation on serum fibrotic markers in chronic hepatitis C (CHC) patients. Fifty-four CHC patients with VD deficiency were randomized into two groups, a VD group (n = 29) and a placebo group (n = 29). The serum levels of 25-hydroxy VD, TGF-β₁, TIMP-1, MMP2 and MMP9 were measured at baseline and at the end of the 6-week study period. Upon correction of VD levels, TGF-β₁ and TIMP-1 levels were decreased, and the MMP2 and MMP9 levels were significantly increased in the VD group. A comparison of the mean changes (delta) in the markers between groups showed that TGF-β₁ and TIMP-1 levels were significantly decreased and the MMP2 and MMP9 were significantly higher in the VD group than in the placebo group. By using CHC patients as a model, this study provides additional evidence that VD plays an important role in the reversal of hepatic fibrogenesis.

Figure 1

Box plot of serum 25(OH)VD at baseline and after VD or placebo supplementation for 6 weeks. White and gray boxes represent median and interquartile ranges at baseline and 6 weeks, respectively. *Numbers that indicate mean ± SD are shown at the top of each time point.

Figure 2

Box plot of mean differences (delta) in serum markers after 6-week supplementation with VD or placebo.

Figure 3

Box plot of serum 25(OH)VD levels and the mean difference in serum TGF- β1 after VD or placebo supplementation for 6 weeks.

Figure 4

CONSORT 2010 flow diagram, CHC patients who were screened, enrolled and monitored. Of 65 patients who were screened for VD deficiency, 7 were excluded, and 58 were randomly assigned to receive placebo or VD supplement; both groups were evaluated after 6 weeks of supplementation.