To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

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.

NCT02484222.

BackgroundChildren with severe obstructive sleep apnea syndrome (OSAS) are more sensitive to opioids. Identifying such children and reducing or even eliminating opioids are necessary but difficult. We have previously shown that patients sensitive to intraoperative fentanyl require less opioids postoperatively.AimThe objective of this study was to evaluate the performance of a postinduction fentanyl test in identifying severe obstructive sleep apnea syndrome.MethodsA prospective, observational, assessor‐blinded study was carried out with 104 sleep study assessed children undergoing elective adenotonsillectomy. Intravenous fentanyl (1 µg/kg) was administered as a test in nonpremedicated, spontaneously breathing, sevoflurane‐induced patients before endotracheal intubation. The respiratory rates before and after fentanyl administration were studied. The primary outcome was the sensitivity and specificity of the postinduction fentanyl test in identifying severe OSAS compared with polysomnography.ResultsA postinduction fentanyl test had a likelihood ratio of 7.2 (95% CI: 3.6‐14.6) and an area under the curve value of 0.896 (95% CI: 0.821‐0.947) to identify severe obstructive sleep apnea syndrome. The pragmatic cut‐off value for the postinduction fentanyl test was found to be 50%. Using a reduction in respiratory rate of >50%, the postinduction fentanyl test detected severe OSAS with a sensitivity of 87%, a specificity of 88%, a positive predictive value of 85%, and a negative predictive value of 89%.ConclusionOur study showed that a postinduction fentanyl test had good predictive value in identifying severe obstructive sleep apnea syndrome and early postoperative adverse respiratory events and could provide a reference for postoperative analgesia in children undergoing adenotonsillectomy.

SummaryWe measured pre-operative hepatic blood flow and postoperative morphine concentration in infants with or without biliary atresia. Thirty-four infants (0-3 months) with biliary atresia undergoing portoenterostomy (Kasai operation) were included and hepatic blood flow was assessed by magnetic resonance imaging before surgery in 12 of them. Sixteen subjects (0-3 months) without liver disease undergoing abdominal or pelvic surgery acted as controls and six of them had hepatic blood flow assessed. Intravenous morphine (8 lg.kg