Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients


  • Potential conflict of interest: Dr. Kronenberger consults, advises, is on the speakers' bureau for, and received grants from Roche, Bristol-Myers Squibb, Gilead, Merck, and Janssen. Dr. Zeuzem consults for and advises Abbott, Achillion, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idmir, Janssen, Novartis, Merck, Presidio, Roche, Santaris, and Vertex.

  • C.M.L. is supported by the Deutsche Forschungsgemeinschaft (LA 2806/2-1), Johann Wolfgang Goethe University (Förderung Nachwuchsforscher 2012), and the Deutsche Leberstifung (S163/10087/2012).

Address reprint requests to: Christian M. Lange, M.D., Department of Internal Medicine 1, Johann Wolfgang Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail: Christian.Lange@kgu.de; fax +49 69 6301 6448


Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB. Of 203 patients, 69 (34%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 <10 ng/mL), vitamin D insufficiency (25(OH)D3 ≥10 and <20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 ≥20 ng/mL), respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels (P = 0.0007 and P = 0.000048, respectively) and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA <2,000 versus ≥2,000 IU/mL were 17 versus 11 ng/mL, respectively (P < 0.00001). In addition, hepatitis B early antigen (HBeAg)-positive patients had lower 25(OH)D3 serum levels than HBeAg-negative patients (P = 0.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations. Conclusion: Low 25(OH)D3 serum levels are associated with high levels of HBV replication in patients with CHB. This represents a major difference from chronic hepatitis C, where numerous previous studies have shown a lack of correlation between HCV viral load and vitamin D serum levels. Inverse seasonal fluctuations of 25(OH)D3 and HBV DNA serum levels are suggestive of a functional relationship between both variables. (Hepatology 2013;58:1270–1276)