The Relationship Between 25-Hydroxyvitamin D 3 and Hepatitis B Surface Antigen Levels in Patients with Chronic Hepatitis B in Japan

Background: Although there are many reports on the relationship between serum 25-hydroxyvitamin D-3 levels and chronic liver diseases, the relevance of the former to the latter is still unclear. Objectives: This study aimed at clarifying the relationship between serum 25-hydroxyvitamin D-3 levels and HBV-related markers, such as HBV-DNA, hepatitis B surface antigen (HBsAg), and hepatitis B virus core-related antigen (HBcrAg) in patients with chronic hepatitis B. Methods: This was a multicenter retrospective study. The subjects consisted of 236 consecutive untreated patients with chronic hepatitis B. Serum 25-hydroxyvitamin D-3 levels were measured by double-antibody radioimmunoassay. The 25-hydroxyvitamin D-3 levels were divided to three groups: <= 20 ng/mL for deficiency, 21 to 29 ng/mL for insufficiency, and >= 30 ng/mL for sufficiency. Results: The subjects consisted of 127 males and 109 females, with a median age of 57 years (range, 15 to 84 years). The patients with positive HBeAg and genotype C accounted for 14.4% and 63.1%, respectively. The median HBV-DNA level and HBsAg level were 684 IU/mL and 750 IU/mL, respectively. The median serum 25-hydroxyvitamin D-3 level was significantly lower in patients (21.0 ng/mL) than in healthy volunteers (25.0 ng/mL, P = 0.013). The median serum 25-hydroxyvitamin D-3 level in patients with a serum HBsAg level >= 1000 IU/mL was significantly lower than that in patients with a serum HBsAg level of < 1000 U/mL (P = 8.06 +/- 10(-3)). The incidence of the HBsAg level >= 1000 IU/mL was 55.8% in patients with vitamin D deficiency and 3 8.2% in patients with vitamin D insufficiency/sufficiency (P = 8.92 x 10(-3)). On multivariate analysis, female gender, the cold season, and a serum HBsAg level of >= 1000 IU/mL were independently associated with vitamin D deficiency. From the opposite viewpoint, vitamin D deficiency and high serum HBcrAg level were independent factors associated with an HBsAg level of >= 1000 IU/mL. Conclusions: This study suggests that serum vitamin D level is closely and negatively correlated with the HBsAg level in chronic hepatitis B patients.