Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2021; 27(3): 255-266
Published online Jan 21, 2021. doi: 10.3748/wjg.v27.i3.255
Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B
Cai-Zhi Huang, Jie Zhang, Lin Zhang, Cui-Hua Yu, Yi Mo, Li-Ya Mo
Cai-Zhi Huang, Jie Zhang, Lin Zhang, Yi Mo, Li-Ya Mo, Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
Cui-Hua Yu, Department of GCP Certified Sites, The Third Hospital of Changsha City, Changsha 410005, Hunan Province, China
Author contributions: All authors contributed to the conceptualization of the study; Mo LY designed the research; Huang CZ and Zhang J performed the research; Zhang L and Yu CH contributed to data collection; Huang CZ and Mo Y analyzed the data; Huang CZ and Mo LY wrote and revised the paper.
Supported by Hunan Provincial Health Commission Science Foundation of China, No. 20200017.
Institutional review board statement: This research was reviewed and approved by Ethics Committee of Hunan Children’s Hospital.
Informed consent statement: Informed consent was obtained from all subjects.
Conflict-of-interest statement: All authors have no conflict of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Li-Ya Mo, MBBS, Chief Technician, Director, Professor, Department of Laboratory Medicine, Hunan Children's Hospital, No. 86 Ziyuan Road, Changsha 410007, Hunan Province, China.
Received: November 4, 2020
Peer-review started: November 4, 2020
First decision: December 24, 2020
Revised: December 29, 2020
Accepted: January 6, 2021
Article in press: January 6, 2021
Published online: January 21, 2021

Vitamin D is an essential fat-soluble secosteroid hydroxylated by the liver to form the intermediate metabolite calcidiol {25-hydroxy vitamin D [25(OH)D]}, which is a reliable indicator to investigate individual vitamin D status. Vitamin-D-binding protein (VDBP) is a multifunctional glycoprotein mainly synthesized in the liver and the major transport protein for vitamin D and its metabolites. Serum vitamin D and VDBP are both associated with hepatitis B. However, few studies have reported the relationship and clinical significance of vitamin D and VDBP with hepatitis B virus (HBV) replication and hepatic fibrosis in children with chronic hepatitis B (CHB).


To explore vitamin D and VDBP serum levels in children with CHB and the association of vitamin D and VDBP with HBV replication and hepatic fibrosis.


We enrolled 204 children with CHB admitted to Hunan Children’ Hospital in summer and autumn between 2018 and 2019 and 170 healthy controls. CHB patients included: 164 hepatitis B e antigen (HBeAg) positive and 40 HBeAg negative; 193 hepatitis B surface antigen (HBsAg) positive and 11 HBsAg negative; 164 with detectable HBV deoxyribonucleic acid (DNA) and 40 with undetectable HBV DNA; 131 with HBV genotype B and 23 with HBV genotype C; and 27 without hepatic fibrosis and 97 with hepatic fibrosis. Serum levels of 25(OH)D, VDBP, liver function markers, and other clinical parameters were collected to analyze their association with vitamin D and VDBP. Mann-Whitney U test, Kruskal-Wallis H test, or t test was used to analyze serum 25(OH)D and VDBP levels in different groups. Spearman rank correlation test was utilized to analyze the correlation of 25(OH)D and VDBP with other markers. Statistically significant factors determined by univariate analysis were further analyzed by binary multivariate logistic regression analysis. P < 0.05 was considered statistically significant.


Children with CHB had lower serum 25(OH)D (56.64 ± 17.89 nmoL/L) and VDBP [122.40 (70.74-262.84 μg/L)] levels than healthy controls had (P < 0.001). Serum 25(OH)D and VDBP levels were significantly different among the different grades of hepatic fibrosis (P < 0.05). VDBP levels in children with HBV genotype C, HBsAg, HBeAg, and detectable HBV DNA were significantly lower than those in children with HBV genotype B, no HBsAg, no HBeAg, and undetectable HBV DNA (P < 0.05). Serum 25(OH)D level was negatively correlated with age and serum total bilirubin level (r = -0.396 and -0.280, respectively, P < 0.001). Serum VDBP level was negatively correlated with HBV DNA (log10 IU/mL) (r = -0.272, P < 0.001). Serum 25(OH)D level was not correlated with VDBP level (P > 0.05). Univariate (P < 0.05) and multivariate logistic regression analysis showed that low level of 25(OH)D (odds ratio = 0.951, 95% confidence interval: 0.918-0.985) and high level of HBV DNA (odds ratio = 1.445, 95% confidence interval: 1.163-1.794) were independently correlated with hepatic fibrosis (P < 0.01).


Serum levels of 25(OH)D and VDBP are decreased in children with CHB. Serum VDBP level is negatively correlated with HBV replication. Low level of 25(OH)D is independently associated with hepatic fibrosis in children with CHB. There is no significant association between serum levels of 25(OH)D and VDBP.

Keywords: Chronic hepatitis B, Children, Vitamin D, Vitamin-D-binding protein, Hepatitis B virus

Core Tip: Serum vitamin D and vitamin-D-binding protein (VDBP) levels are associated with hepatitis B. The association of vitamin D and VDBP with hepatitis B virus replication and hepatic fibrosis in children with chronic hepatitis B (CHB) has rarely been reported. We found that low level of serum 25-hydroxy vitamin D is an independent factor associated with development of hepatic fibrosis, and it could be valuable for maintaining sufficient 25-hydroxy vitamin D level to prevent or delay hepatic fibrosis in children with CHB. VDBP is negatively correlated with hepatitis B virus replication, and VDBP analogs might be considered for management of CHB.