Vitamin D serum level is associated with Child-Pugh score and metabolic enzyme imbalances, but not viral load in chronic hepatitis B patients

Vitamin D deficiency is common in patients with chronic liver diseases. However, vitamin D status in persons with chronic hepatitis B virus (HBV) infection is not consistently reported. Specifically, the impact of liver dysfunction on vitamin D status has not been well addressed. We recruited a group of patients (n = 345) with chronic hepatitis B (n = 115), hepatitis B related cirrhosis (n = 115), and age-and gender-matched healthy controls (n = 115). Serum 25-hydroxyvitamin D3 [25(OH)D3], its related metabolic enzymes, intact parathyroid hormone were measured. Calcium, magnesium, and phosphorus were obtained from medical record. Serum 25(OH)D3 levels in chronic hepatitis B patients (7.83 +/- 3.47ng/mL) were significantly lower than that in healthy controls (9.76 +/- 4.36 ng/mL, P < 0.001), but significantly higher than that in hepatitis B-related cirrhotic patients (5.21 +/- 3.67ng/mL, P < 0.001). Furthermore, 25(OH)D3 decreased stepwise with higher Child-Pugh classification. However, there were no significant differences in 25(OH)D3 levels between (1) hepatitis B e antigen (HBeAg +) and HBeAg(-) persons, or (2) among persons with different HBV viral load, or (3) between treatment naive and patients on antiviral therapy. Multiple logistic regression analyses confirmed that higher Child-Pugh score was independently associated with 25(OH)D3 deficiency (< 10ng/mL) with an odds ratio of 1.20 (confidence interval 1.03-1.39, P = 0.016). Levels of cytochrome P450 (CYP) 27A1 were significantly decreased, whereas levels of CYP24A1 were significantly elevated in cirrhotic patients. These results suggest that decreasing vitamin D levels are likely to be a result, rather than a cause, of liver dysfunction and irrespective of HBV viral load. Reduction in 25(OH)D3 levels is possibly due to downregulation of the synthetic hydroxylase CYP27A1 and concurrent upregulation of degrading CYP24A1 in patients with liver cirrhosis.