Effect of vitamin D supplementation in patients with chronic hepatitis C after direct-acting antiviral treatment: a randomized, double-blind, placebo-controlled trial

Background: Replacement of vitamin D (VD) among patients with
chronic hepatitis C (CHC) before viral eradication has demonstrated a
protective effect on serum markers associated with hepatic fibrogenesis.
We therefore hypothesized that VD may facilitate further fibrosis
amelioration following curative treatment with direct-acting antivirals
(DAA).  Methods: This study was a randomized,
double-blind, placebo-controlled trial conducted between February 2018 and
August 2018. Patients with CHC and VD deficiency were randomized in a 1:1
ratio to either receive ergicalciferol or placebo over 6 weeks.
Biochemical analysis indicators, including 25-hydroxyvitamin D (25(OH)D),
fibrogenic markers [(transforming growth factor beta 1 (TGF-β1) and tissue
inhibitors of matrix metalloproteinases 1 (TIMP-1)], and fibrolytic
markers [matrix metalloproteinase 9 (MMP-9) and amino terminal type III
procollagen peptide (P3NP)], were assessed at baseline and at 6 weeks.
Serum 25(OH)D was analyzed by a chemiluminescence immunoassay. Serum
hepatic fibrogenesis markers were measured using a quantitative sandwich
enzyme-linked immunosorbent assay. Results: Seventy-five patients
with CHC and VD deficiency were randomly assigned to VD (n=37) and placebo
(n=38) groups. At the end of the study, the mean serum 25(OH)D level had
risen to a normal level in the VD group, but was still deficient in the
placebo group (41.8±9.1 vs. 18.1±4.6 ng/mL, p<0.001). Upon
restoration of the VD level, there were no significant mean differences in
the change from baseline for TGF-β1 (-0.6 ng/mL (95% confidence interval
(95%CI) -2.8 – 1.7), p=0.63), TIMP-1 (-5.5 ng/mL (95%CI -26.4 – 15.3),
p=0.60), MMP-9 (122.9 ng/mL (95%CI -69.0 – 314.8), p=0.21), and P3NP (-0.1
ng/mL (95%CI -2.4 – 2.2), p=0.92) between the VD and placebo
groups.  Conclusion: Short-term VD supplementation after
DAA treatment in patients with CHC does not improve serum fibrogenesis
markers and may not expedite the residual liver fibrosis healing process.
Future studies are warranted to evaluate the long-term effect of VD
supplementation on hepatic fibrosis regression.