Associations between Vitamin D and Liver Function and Liver Fibrosis in Patients with Biliary Atresia

Abstract

Objectives To detail the effects of vitamin D (VD) deficiency and assess the relationships between VD deficiency and liver function and liver fibrosis in patients with biliary atresia (BA). Methods In this study, BA patients confirmed by intraoperative cholangiography were enrolled between January 2017 and February 2019. Preoperative serum 25-(OH)D level, liver function, serum biomarker levels of liver fibrosis, and histopathologic features were recorded. Deficiency, insufficiency, and sufficiency of VD were defined as serum 25-(OH)D concentrations of <10, 10-20, and >20 ng/ml, respectively. Associations between serum 25-(OH)D level and liver function and liver fibrosis were analyzed. Results A total of 161 BA infants were included. The median (interquartile range (IQR)) serum 25-(OH)D level in all patients was 7.56 (IQR: 4.48–11.40) ng/ml. The rates of 25-(OH)D deficiency, insufficiency, and sufficiency were 67.1% (108/161), 29.2% (47/161), and 3.7% (6/161), respectively. Serum 25-(OH)D level was negatively correlated with alkaline phosphatase (r = ‐0.232, P = 0.003). After adjusting for age, a decrease in serum 25-(OH)D level was correlated with the increase of the Batts-Ludwig stage score (odds ratio (OR): 0.94, 95% confidence interval (CI): 0.88–0.99; P = 0.028). Serum 25-(OH)D level was also correlated with the N-terminal propeptide of type III procollagen (PIIINP) (r = ‐0.246, P = 0.002). Additionally, PIIINP (P = 0.038) and ALP (P = 0.031) were independently associated with serum 25-(OH)D level. Conclusions VD deficiency was common and inversely correlated with liver fibrosis in BA patients. Furthermore, VD was not correlated with liver function except alkaline phosphatase.

Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

“…Previous animal studies have confirmed that the binding of active vitamin D and VDR can regulate activity of the TGF-β signaling pathway in HSCs, thereby inhibiting expression of fibrosis genes and expression 28 , 31 and deposition of types I and III collagen 30 , 41 . A recent study found that serum N-terminal peptide of procollagen III, an indicator of liver fibrosis, was negatively correlated with 25(OH)D in children with BA 35 . At present, there has been no study on the mechanism of 25(OH)D deficiency in BA, nor on the mechanism of the relationship with liver fibrosis.…”

“…In recent years, as more studies have gradually revealed the internal relationship between vitamin D deficiency and liver fibrosis, researchers have begun to pay attention to this problem. Ng et al 34 detected the pre-HPE 25(OH)D level in 92 children with BA, and found that 98.9% of the children had 25(OH)D deficiency or insufficiency, and only one (1.1%) had a normal level of 25(OH)D. Zhuang et al 35 examined the 25(OH)D level before HPE of 161 BA cases, and found that 96.3% of the children had 25(OH)D deficiency or insufficiency. However, these studies confirmed deficiency of 25(OH)D in children with BA, but did not further investigate the cause of that deficiency and its effect on liver lesions.…”

“…Whether the active vitamin D deficiency and activation disorder in BA are involved in the pathological process of liver fibrosis has not been researched to date, even though a correlation between 25(OH)D deficiency and liver fibrosis in BA has been confirmed in several clinical studies. Zhuang et al 35 examined the level of 25(OH)D in 161 children with BA and staged liver fibrosis in pathological specimens, and found that 25(OH)D level was negatively correlated with the stage of liver fibrosis. Peng et al 39 studied the correlation between 25(OH)D level and liver shear wave elastography in 33 children with BA after HPE, and found that 25(OH)VD level was negatively correlated with liver fibrosis severity.…”

Prevalence of Fat-Soluble Vitamin Deficiency in Post Hepaticoportoenterostomy Biliary Atresia Patients

“…A decrease in an inhibitory signal on the TGF-beta/SMAD-dependent transcriptional response of pro-brotic gene in the hepatic stellate cells has been postulated as a pathogenesis link. [10][11][12] An animal model study also showed that vdr −/− mice developed more bile duct injury by losing bile duct epithelial polarity after bile duct ligation compared to the wild-type strains. [13] Moreover, a clinical observational study demonstrated a negative correlation between vitamin D levels and NAFLD brotic score.…”