DOI: 10.5061/dryad.573n5tb4h
title: Effect of vitamin D supplementation in patients with chronic hepatitis C after direct-acting antiviral treatment: a randomized, double-blind, placebo-controlled trial

description: 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&lt;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.
description: This randomised, double-blind, placebo-controlled study was
 conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand from
 February 2018 to August 2018. All patients with CHC who achieved SVR
 within 1 year after DAA therapy in the hepatology clinic were assessed for
 eligibility. Baseline clinical characteristics, HCV genotypes, liver enzymes, and FIB-4 and APRI scores were assessed. Blood samples were collected at baseline and at the end of the 6-week follow-up and were kept at −70°C until analysis. All blood samples were simultaneously analysed for TGF-ß1, TIMP-1, MMP-9, and P3NPlevels at the end of the study. Pill counts and patient interviews were used to assess adherence to the prescribed medications. All participants were asked to refrain from outside-of-trial vitamin D or multivitamin supplements and to maintain their normal activity. At the end of the study, patients who remained in a VD insufficient state received VD supplementation as a standard of care.