Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial

Abstract

Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC.

Trial registration: Thai Clinical Trials Registry TCTR20160429001.

Fig 1. CONSORT 2010 flow diagram.

CHC patients who were enrolled and followed up. 93 patients were screened for participation in the study. 13 patients were excluded. 80 patients were randomly assigned to receive a placebo or vitamin D supplements and followed up after six weeks of supplements. BMJ 2010;340:c869. doi:10.1136/bmj.c869.

Fig 2. Mean changes of vitamin D levels.

(A), IP-10 (B) and DPP IV (C) levels after 6-week supplements in placebo and vitamin D groups were demonstrated. The x-axis of each graph represents mean changes of the levels (delta). The blue and orange boxes represent placebo group and vitamin D group, respectively.

Fig 3. Scatter plot of post treatment VD levels (x-axis) and post treatment IP-10 level (y-axis) including fit line and regression equation were demonstrated.