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

Hepatology. 2013 Oct;58(4):1270-6. doi: 10.1002/hep.26488. Epub 2013 Aug 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Cohort Studies
  • DNA, Viral / blood
  • Female
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Viral Load / physiology
  • Virus Replication / physiology*
  • Vitamin D / blood*


  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Vitamin D