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

Randomized, double-blind, placebo-controlled trial in chronic hepatitis C patients with vitamin D deficiency; 58 participants aged 26–70 years (mean 50.3 ± 10.6); 36 male (62.1%), 22 female (37.9%); included as naïve or non-responder CHC without decompensated cirrhosis; 29 per group.

Vitamin D2 (ergocalciferol) oral capsules; duration 6 weeks; weekly total doses based on baseline 25(OH)VD: 60,000 IU/week (2 × 20,000 IU capsules on Monday + 1 × 20,000 IU on Friday) for 20–29 ng/mL; 80,000 IU/week (2 × 20,000 IU capsules on Monday + 2 × 20,000 IU capsules on Friday) for 10–19 ng/mL; 100,000 IU/week (3 × 20,000 IU capsules on Monday + 2 × 20,000 IU on Friday) for <10 ng/mL.

25(OH)VD rose from 19.9 ± 5.3 to 45.6 ± 12.6 ng/mL (p<0.001) in the vitamin D group; placebo showed no significant change (18.6 ± 5.1 to 18.2 ± 5.5 ng/mL; p=0.3). Compared with placebo, the vitamin D group had a fibrolytic shift: TGF-β1 decreased (−24.6 ± 113.1 pg/mL vs +57.1 ± 107.4 pg/mL; p=0.0117), TIMP-1 decreased (−0.40 ± 0.16 vs +0.30 ± 0.70 ng/mL; p=0.0194), MMP2 increased (+51.7 ± 121.3 vs −41.9 ± 128.6 ng/mL; p=0.0146), MMP9 increased (+34.2 ± 38.5 vs −23.3 ± 26.6 ng/mL; p<0.0001). ALT decreased in the vitamin D group (−38.1 ± 70.5 U/L; p=0.02); HCV RNA did not change. Between-group delta differences were significant for all four markers (p<0.05). Interpretation: restoring VD to normal levels may contribute to reversal of hepatic fibrogenesis in CHC based on serum markers; long-term clinical fibrosis outcomes require further study.

Outcomes based on serum fibrosis markers rather than liver histology; short duration (6 weeks); small sample size; no long-term fibrosis data; potential baseline variability; generalizability limited to CHC with vitamin D deficiency.