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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.

BACKGROUNDS AND AIMS: Proton-pump inhibitor is more effective for gastric acid control in Asian than Western population possible because of high prevalence of poor metabolizing CYP2C19 genotype in Asian people. The aim of this study was to evaluate the effect of low dose intravenous (IV) bolus vs. standard recommended dose continuous IV infusion of omeprazole in Thai healthy volunteers with extensive metabolizing CYP2C19 genotype. METHODS: 8 healthy subjects (age 30±6yr, 5 F, BMI 24±3 kg/m2) with extensive metabolizing CYP2C19 genotype were randomized to receive either omeprazole 80mg IV bolus followed by 40 mg IV bolus every 12 hr or omeprazole 80mg IV bolus followed by 8mg/ hr continuous infusion for 48 hr. The gastric pH was monitored by a pH catheter with a data logger (DIGITRAPPER pH 400, Medtronic A/S) for 2 days during the omeprazole treatment peroids. The gastric pH sensor was positioned at 10 cm below the lower esophageal sphincter located by esophageal manometry. All subjects were allowed to consume 3 standard meals/day. RESULTS : The mean gastric pH for IV bolus was significantly lower than continuous infusion only on day 1 [6.2±1.0 vs. 7.1±0.6 (p 6 for IV bolus was also significantly lower compared to continuous infusion only on day 1(66.2±22.7% vs. 84.7±17.3%)(p 6 for the entire 48-hr study was significantly lower for IV bolus compared to continuous infusion (69.9±12.6% vs. 83.0±13.8%, p 24 had similar intragastric pH during both IV bolus and IV continuous infusion of omeprazole (IV bolus, BMI 24: 6.4±0.9 vs. 6.3±0.4) (continuous drip; 7.1±0.3 vs. 6.8±0.6)(p>0.05). CONCLUSION: Continuous IV infusion of standard recommended dose of omeprazole provided better gastric acid control compared to lower dose IV bolus only during the first day but not on the second day. Although the continuous IV infusion was more effective both standard dose continuous IV infusion and low dose IV bolus omeprazole was effective for gastric pH control in Thai healthy volunteers with extensive metabolizing CYP2C19 genotypes. The better gastric acid control compared to those reported in healthy volunteers in Western countries suggests the role of other factor(s), beside the CYP2C19 genotype, on gastric acid inhibition effect of IV omeprazole.