The Hepatic Expression of Vitamin D Receptor is Inversely Associated with the Severity of Liver Damage in Genotype 1 Chronic Hepatitis C Patients.

Abstract

Background/aims: Low 25-Hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity. Methods: Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by western blot for quantification, and by immunohistochemistry for morphological distribution. Results: Liver VDR protein was mainly localized in hepatocytes and cholangiocytes, and its expression by western blot was similar in CHC and controls (1.83±0.97 vs. 2.18±0.62, p=0.14), but lower in autoimmune hepatitis (0.84±0.14, p<0.001). The expression was lower in CHC with severe necroinflammatory activity (1.44±0.87) vs. both controls and CHC with grade 1-2 inflammation (1.94±0.97)(p=0.01 and p=0.03, respectively), but higher compared to autoimmune hepatitis (p=0.007). A similar difference was observed in CHC patients with F3-F4 fibrosis, whose VDR expression (1.51±1.07) was also lower compared with controls and CHC with F0-F2 fibrosis (1.98±0.89)(p=0.02 and p=0.04, respectively), but higher vs. autoimmune hepatitis (p=0.003). At multivariate logistic regression analysis, low VDR protein expression remained associated with severe necroinflammatory activity and severe fibrosis (OR 0.543,95%CI, 0.288-0.989, p=0.04; and OR 0.484,95%CI 0.268-0.877, p=0.01, respectively) in CHC after correction for clinical, biochemical and histological features. Conclusion: In a cohort of G1CHC patients, the hepatic expression of VDR protein is associated with the severity of both liver fibrosis and inflammation.