Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B

Abstract

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.