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Research Article
Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B
Henry Lik-Yuen Chan1, , Magdy Elkhashab2, Huy Trinh3, Won Young Tak4, Xiaoli Ma5, Wan-Long Chuang6, Yoon Jun Kim7, Eduardo B. Martins8, Lanjia Lin8, Phillip Dinh8, Prista Charuworn8, Graham R. Foster9, Patrick Marcellin10
Background & Aims
The relationship between vitamin D levels and chronic hepatitis B (CHB) infection and treatment outcomes are poorly elucidated. We measured pre-treatment serum vitamin D (25-hydroxyvitamin D3; 25[OH]D3) levels and determined their association with clinical parameters and treatment outcomes in active CHB patients without advanced liver disease enrolled in a global clinical trial.
Methods
Patients were randomly assigned to either 48 weeks of tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2a (PegIFN), TDF plus PegIFN for 16 weeks followed by TDF for 32 weeks, PegIFN for 48 weeks, or TDF for 120 weeks. Univariate and multivariate analyses were conducted to determine associations between vitamin D, baseline factors, and week 48 clinical outcome.
Results
Of 737 patients, 35% had insufficient (⩾20 but <31 ng/ml) and 58% had deficient (<20 ng/ml) vitamin D levels. In univariate analysis, lower vitamin D levels were significantly associated with the following baseline parameters: younger age, lower uric acid levels, HBeAg-positive status, lower calcium levels, blood draw in winter or autumn, and HBV genotype D. On multivariate analysis, only HBV genotype, season of blood draw, calcium level, and age retained their association. High baseline level of vitamin D was associated with low HBV DNA, normal ALT and HBsAg at week 48 independent of treatment groups, but the association, with the exception of ALT, became statistically insignificant after adjusting for age, gender, HBeAg and HBV genotype.
Conclusions
Abnormally low vitamin D levels are highly prevalent among untreated, active CHB patients. Baseline vitamin D levels are not associated with treatment outcomes, but were associated with normal ALT.
Abbreviations
CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; TDF, tenofovir disoproxil fumarate; HBV, hepatitis B virus; 25[OH]D, 25-hydroxyvitamin D3; HCV, hepatitis C virus; ISG, interferon-stimulating gene; PegIFN, pegylated interferon-α 2a; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TSH, thyroid-stimulating hormone; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody
Keywords
Hepatitis B; Seasonal variation; Tenofovir disoproxil fumarate; Vitamin D deficiency
Corresponding author. Address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved.
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