Biliary Atresia Patients Research Articles

Health-Related Quality of Life in Biliary Atresia Patients with Native Liver or Transplantation.

We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL. We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire. We compared HrQoL scores in BA patients with healthy peers and with children who had undergone major surgery in infancy or children with chronic conditions. We determined the relationship between specific patient-related factors and HrQoL. Literature data indicated that HrQoL in children with BA is lower than in healthy peers. In Dutch BA patients (n = 38; age 10 ± 3 years), parent-proxy physical HrQoL (48 ± 11) was significantly lower compared with two reference groups of healthy peers (59 ± 4 and 56 ± 6, respectively, each p < 0.001), and lower than in children with attention deficit hyperactivity disorder (60 ± 5), asthma (54 ± 6), attending a cardiology clinic (52 ± n/r), congenital diaphragmatic hernia (53 ± 7) or D-transposition of the great arteries (54 ± 6; all p < 0.05). Psychosocial HrQoL (50 ± 9) was lower than in healthy peers (54 ± 6, p = 0.02, and 53 ± 6, p = 0.07) and children with asthma (54 ± 6, p = 0.02), and largely comparable to children with other chronic conditions. Parent-proxy physical HrQoL was adversely related to adverse medical event in the past year, special education, and motor impairments; psychosocial HrQoL was adversely related to behavioral problems. Children with BA are at risk of impaired HrQoL. Special attention is warranted for children with adverse medical events and special education.

Validating the BAVENO VI criteria to identify low risk biliary atresia patients without endoscopy for esophageal varix

Portoenterostomy is the initial surgical treatment for biliary atresia (BA); however, no curative therapy exists for BA. Varix bleeding is a major complication of end-stage liver disease and must be determined in patients with BA, necessitating routine surveillance using esophagogastroduodenoscopy (EGD). We attempted to validate criteria to identify BA patients requiring EGD. From January 2007 to December 2017, we selected BA patients who underwent Kasai surgery, transient elastography (TE), and EGD at Severance hospital. In total, 190 cases were included; laboratory tests and EGDs were carried out from 3 months before TE to 3 months after TE. Based on the cut-off value (<10) of the liver stiffness measurement (LSM), 35 (81.4%) patients with low-risk varix (LRV) and 8 (18.6%) with high-risk varix (HRV) were identified. Based on platelet counts (>150,000), 87 (77.68%) patients with LRV and 25 (22.32%) with HRV were identified. Based on this, the BAVENO VI criteria, which identify patients who can safely avoid screening EGD, missed 9/68 (13.24%) of HRV patients. The expanded BAVENO VI criteria missed 21/68 (30.88%) of HRV patients. However, the criteria using LSM <10 and platelet count >150,000 missed identifying only 4/68 (5.88%) HRV patients. The BAVENO criteria may be as useful in children with BA as in adults with liver cirrhosis. Regular laboratory tests, imaging studies, and EGD may avoid missing diagnoses of varices in BA patients. However, LSM<10 and platelet count>150,000 may provide more accurate criteria and help identify patients who does not need endoscopy.

Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility.

Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of ADD3, GPC1, ARF6, and EFEMP1 gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population. Twenty single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 340 BA patients and 1,665 controls. Three SNPs in ADD3 were significantly associated with BA, and rs17095355 was the top SNP (PAllele = 3.23×10-6). Meta-analysis of published data and current data indicated that rs17095355 was associated with BA susceptibility in Asians and Caucasians. Three associated SNPs were expression quantitative trait loci (eQTL) for ADD3. Two GPC1 SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility (PAllele = 0.03 for rs6707262 and PAllele = 0.04 for rs6750380), and were eQTL of GPC1. Haplotype harboring these two SNPs almost reached the study-wide significance (P = 0.0035). No association for ARF6 and EFEMP1 was found with BA risk in the current population. Our study validated associations of ADD3 and GPC1 SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.

The duodenal tube test is more specific than hepatobiliary scintigraphy for identifying bile excretion in the differential diagnosis of biliary atresia.

Confirmation of bile excretion into the gastrointestinal tract is important to exclude biliary atresia (BA). We compared the duodenal tube test (DTT) with hepatobiliary scintigraphy (HS) for their efficiency in detecting bile secretion. The subjects of this retrospective study were 47 infants who underwent both DTT and HS to diagnose or exclude BA between January 2000 and March 2018. BA was diagnosed in 32 of the 47 patients, and 7 of the remaining 15 non-BA patients underwent intraoperative cholangiography. Among the various DTT parameters, the total bile acid in duodenal fluid (DF-TBA)/serum (S) gamma-glutamyl transferase (γGTP) ratio was found to be the most specific for BA, with sensitivity and specificity of 98.0-100%, respectively. One BA patient in whom cut off values were not met was a premature infant. The sensitivity and specificity of HS were 100-56.3%, respectively. The diagnostic accuracy of the DF-TBA/S-γGTP parameter was higher than that of HS (98.6% vs. 85.1%, respectively). The DTT could be more a specific method than HS to detect bile excretion. Thus, the DTT should be incorporated into the multidisciplinary diagnostic approach for the differential diagnosis of BA to prevent unnecessary intraoperative cholangiography in patients who do not have BA.

Factors Related to the Clinical Outcomes of the Kasai Procedure in Infants with Biliary Atresia

Objective: The Kasai portoenterostomy has been accepted as the primary therapeutic treatment for biliary atresia. However, successful bile drainage does not always promise a long-term native liver survival. Several clinical factors were evaluated to discover associations with the outcomes.Methods: A retrospective chart review was conducted of infants with biliary atresia who underwent the conventional Kasai portoenterostomy at Siriraj Hospital, January 2006-August 2018. The patient demographics, perioperative clinical and laboratory data, adjuvant therapies, complications, and interventions were analyzed in correlation to the short- and long-term outcomes. The short-term outcome evaluated was the resolution of jaundice, while the long-term outcome was remaining jaundice-free with the native liver.Results: The complete medical records of 80 patients were retrospectively reviewed. Their mean age at the time of the Kasai portoenterostomies was 97 days. Overall, 66.3% achieved jaundice clearance. The mean follow-up duration was 50.5 months, with 51.3% of the patients remaining jaundice-free with their native liver. A prolonged duration of a prophylactic antibiotic was significantly related to the jaundice clearance, with a p-value of 0.002. Moreover, a lower number of episodes of cholangitis was significantly related to a good long-term outcome (p-value, 0.024).Conclusion: The prolonged provision of a prophylactic antibiotic as adjuvant therapy after the Kasai portoenterostomy was associated with jaundice clearance. An increased incidence of cholangitis episodes was associated with poor long-term outcomes. Postoperative adjuvant therapy should be standardized and maintained for the care of biliary atresia patients to improve their outcomes.

The short-term outcome of modified laparoscopic Kasai portoenterostomy for biliary atresia.

Laparoscopic Kasai portoenterostomy (LKPE) has been shown to be a safe and feasible procedure in patients with biliary atresia (BA). The purpose of this study was to investigate the efficacy of modified LKPE (MLKPE) in the treatment of BA. Data of 58 BA patients undertaken MLPKE from July 2014 to December 2015 were retrospectively analyzed (group B), and compared with that of 43 BA patients received open Kasai portoenterostomy (OKPE) during the same period (group C). In addition, 195 BA patients who had undergone LKPE during May 2009 to June 2014 were also included (group A). All 296 patients enrolled in this study were non-syndromic type III BA. Compared with group A, group B had shorter operative time (ORT) (P < 0.01) and fewer intraoperative blood transfusion (IOBT) (P < 0.05). The conversion rate and cholangitis rate were also significantly lower in group B than that in group A (P < 0.05). The postoperative oral intake resumed (POOR), any postoperative complications (APOC), clearance of jaundice (CJ), 1-year and 3-year survival rate with native liver (SNL) were not significantly different between group A and group B (P > 0.05). The ORT, IOBT, POOR, APOC, CJ, 1-year and 3-year SNL in group B were much better than that of group C (P < 0.05). The MLKPE was associated with good perioperative with ORT, IOBT, POOR, and APOC. The short-term outcomes in MLKPE were no worse than that of OKPE and LKPE. MLKPE can be regarded as a treatment option for BA.

Hepatic expression of HGF/C-met and native liver survival in biliary atresia.

The prognosis of biliary atresia (BA) remains difficult to predict. This study evaluated the roles of hepatocyte growth factor (HGF) and its receptor (C-met) towards clinical outcome and native liver survival. Hepatic HGF and C-met expression were determined using immunohistochemistry from liver biopsies of 41 BA patients during Kasai operation, and 17 non-cholestatic patients. The HGF and C-met expression was visually scored as per its intensity and percentage of stained area. BA patients were classified as high- and low-HGF and C-met receptor status. Native liver survival was compared between the two groups at 3-year follow-up. Data are shown as median and range. Median age of BA patients was 2 (1-6) months. Hepatic HGF and C-met staining scores of BA patients were higher than those of non-cholestatic patients (P < 0.0001). There was a correlation between HGF and C-met staining scores (spearman r = 0.77, P < 0.0001). However, there was no association between their expression and early outcome at 6months post-op. Mean follow-up time was 68.6months. Survival analysis revealed that native liver survival at 1year and 3years were 88% and 77%, respectively. Additionally, 82.6% (19/23) of patients in the low-HGF group survived with native liver, compared with 66.7% (10/15) of those in high-HGF group (P = 0.436). For C-met expression, 78.6% (22/28) of low-score and 70% (7/10) of high score groups survived with native liver (P = 0.673). Strong expression of hepatic HGF and its receptor in BA patients was demonstrated. However, the expression was not associated with the early outcome and native liver survival. These results suggest that HGF involved in the liver pathology of BA but its expression cannot be used as a prognostic indicator. Small sample size of patients was a main limitation. Further studies are warranted to validate our findings.

Biliary Atresia Patients With Successful Kasai Portoenterostomy Can Present With Features of Obliterative Portal Venopathy.

Study of liver explants of biliary atresia (BA) patients with successful Kasai portoenterostomy (KP). Pathology and medical records of BA liver explants from January 2009 to June 2018 with successful KP were reviewed along with appropriate controls. Fourteen out of 68 (20.6%) BA patients with LT had a successful KP. Median age at BA diagnosis, KP and LT was 60.5 days, 61 days, and 10 years, respectively, with conjugated bilirubin (c-bil) normalizing at 12.5 weeks after KP. Advanced fibrosis was diffuse in 2/14 (14.3%) explants, limited to periphery in 11/14 (78.6%) and absent in 1. Hilar partial nodular transformation (PNT) was seen in 11 explants (78.6%) and diffuse nodular regenerative hyperplasia (NRH) in 2 (14.3%). Areas of PNT and NRH showed diffuse portal sclerosis (100%), complete and incomplete portal vein (PV) stenosis (100%), PV herniation (100%), hypervascular portal tracts (20%), periportal abnormal vessels (100%), abundant lymphatic collaterals (100%), mild medial hepatic arterial hypertrophy (100%), and delicate fibrous septae (100%). Extrahepatic PVs showed variable luminal occlusion with mean PV intima to full thickness ratio of 0.6 +/- 0.11; significantly higher than age-matched noncirrhotic (n = 27, 0.08 +/- 0.09; P < 0.0001) and cirrhotic controls (n = 19, 0.34 +/- 0.2; P = 0.0015); and comparable to BA patients with failed KP (P = 0.82) and without KP (P = 0.04). BA patients with successful KP can present with obliterative portal venopathy (OPV). In the context of optimal bile drainage, portal hypertension may not be because of advanced parenchymal fibrosis but possibly because of OPV. Vascular abnormalities of the PV system should be investigated in BA patients.

Hepatic Subcapsular Flow as a Significant Diagnostic Marker for Biliary Atresia: A Meta-Analysis.

Aim Increasing evidence indicates that hepatic subcapsular flow (HSF) can serve as a noninvasive ultrasonographic marker for the early diagnosis of biliary atresia (BA). However, results regarding its diagnostic accuracy are inconsistent and inconclusive. We conducted this meta-analysis with an aim to systematically evaluate the diagnostic value of HSF in predicting BA. Methods A comprehensive literature search of four databases was conducted to identify the eligible studies. All analyses were performed using STATA 12.0. Results Nine studies from eight articles containing 368 patients and 469 controls were included in our meta-analysis. Briefly, the values for pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.95 (95% CI 0.88-0.98), 0.92 (95% CI 0.85-0.96), 11.6 (95% CI 6.3-21.5), 0.06 (95% CI 0.02-0.14), 201 (95% CI 59-689), and 0.98 (95% CI 0.96-0.99), respectively. Additionally, metaregression along with subgroup analysis based on various covariates revealed the potential sources of heterogeneity and the detailed diagnostic value in each subgroup. Conclusion Our meta-analysis showed that HSF assay could provide high accuracy in predicting BA patients and non-BA individuals. However, further studies with better design and larger sample size are required to support the results of the present study.

Irrelevance of USF2 rs916145 polymorphism with the risk of biliary atresia susceptibility in Southern Chinese children.

Backgrounds: Biliary atresia (BA) is a very rare neonatal disease, however, it has been the most common cause of obstructive jaundice in infancy. The complex pathogenesis of BA is not entirely clear and a lot of possible pathogenic mechanisms have been proposed to explain the etiology of BA, including genetic, inflammatory, environmental and developmental abnormalities. As a transcription factor, USF2 gene rs916145 polymorphism has been shown to be related to the risk of BA.Methods: We examined the USF2 rs916145 genotype in a large case–control study consisting of 506 BA patients and 1473 healthy controls, using the MassARRAY iPLEX Gold system (Sequenom). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the USF2 gene rs916145 polymorphism and BA susceptibility.Results: The frequency of different genotypes showed no statistical significance (GG/GC, OR: 1.09, P=0.470, 95% CI: 0.87–1.35; GG/CC, OR: 0.86, P=0.378, 95% CI: 0.62–1.20). No obvious association was revealed between the USF2 gene rs916145 polymorphism and BA susceptibility.Conclusion: USF2 rs916145 polymorphism may not be the best predictor of BA.

Repeatability and Reliability of Home-Based Stool Color Card Screening for Biliary Atresia Based on Results in China and Japan.

Biliary atresia (BA) is the most frequent hepatic cause of death in early childhood. Early referral and timely Kasai portoenterostomy are essential for the improvement of long-term native liver survival rate of BA patients. Screening with stool color card (SCC) has been implemented in Japan since 1994. Recently current digital edition of SCC consisted of seven digitally created images was introduced to China. Our study aimed to evaluate the repeatability and reliability of same edition of SCC used in Beijing, China and Sapporo, Japan. In Beijing from 2013 to 2014, SCCs were distributed to infants' guardians by trained nurses in maternal facilities during information sessions on neonatal screening programs. SCC was used at three checkpoints for each infant after birth for screening. The SCC data were collected from 27,561 infants (92.5%) in Beijing by 42-day health checkup, mobile phone and social network services. In Sapporo from 2012 to 2015, the SCCs with a postcard and guardian instructions were inserted into Maternal and Child Health Handbook and distributed to all pregnant women. The data were collected from a total of 37,478 (94.3%) infants in Sapporo via the postcard during the 1st month infant health checkup. We thus identified two BA patients in Sapporo and two BA patients in Beijing. High rates of sensitivity and specificity in both cities were observed. The frequency distribution of color images on SCC reported in both cities was similar. This study shows excellent repeatability and reliability of the current digital edition of SCC.

Evaluation of serum levels of trace elements in children with biliary atresia and their correlation with liver histopathology

Background:Children with biliary atresia (BA) have impaired metabolism of trace elements (TEs) (i.e., zinc, copper, selenium, and manganese), leading to an alteration in the serum levels. However, this alteration in serum level has any correlation with liver histopathological changes is not yet clear.Materials and Methods:This prospective study attempts to evaluate the preoperative serum levels of TE in comparison to controls and its correlation with liver histology in children with BA. Kasai portoenterostomy (KPE) and liver biopsy were performed in all cases. On liver histology, various parameters assessed and were graded according to predefined criteria. Serum levels of TE were determined again 12 weeks post-KPE and compared with the preoperative levels.Results:Mean(±standard deviation [SD]) preoperative serum Zn, Cu, Se, and Mn levels (in μg/dl) in BA patients were 41.6 ± 12.8, 130.6 ± 12.8, 50.0 ± 10.0, and 32.0 ± 20.0, respectively; in controls, these levels were 77.9 ± 13.7, 133.7 ± 13.7, 87.0 ± 13.0, and 8.0 ± 5.5, respectively. Mean postoperative levels in all patients were 68.5 ± 19.0, 91.7 ± 19.0, 79.0 ± 19.0, and 28.0 ± 12.0, respectively. Mean(±SD) postoperative serum Zn, Cu, Se, and Mn levels in BA patients with bile excretion were 73.8 ± 14.9, 83.6 ± 13.8, 85.0 ± 15.0, and 26.0 ± 10.0, respectively, whereas in those with no bile excretion, they were 40.6 ± 12.8, 134.0 ± 23.0, 49.0 ± 11.0, and 44.0 ± 16.0, respectively. In liver histology, specific parameters showed correlation with high Mn and low Zn levels.Conclusion:Serum TE levels are altered in children with BA and the establishment of successful biliary drainage may change the subsequent postoperative serum concentration. Serum Zn and Mn levels can signify specific histopathological liver changes and the extent of liver damage.

Whole exome sequencing analysis for mutations in isolated type III biliary atresia patients.

Aim of the studyBiliary atresia is an idiopathic, destructive disease that affects both extrahepatic and intrahepatic bile ducts with severe inflammation and manifests as progressive jaundice within the first few months of life. In this study, we aimed to investigate the significance of genetic mutations in the onset of biliary atresia disease.Material and methodsWith the approval of the ethics committee and parental consent, blood was taken from patients to obtain their DNA, and the study commenced. In this prospective study, we examined the DNA of 10 patients with no disease other than biliary atresia, and an exome sequence analysis was performed with the new-generation DNA sequencing method. The genetic structure of biliary atresia disease was examined by statistical analysis of the mutations, which were determined according to the reference DNA sequencing.ResultsIn the exome sequence analysis, the number of mutations detected among the patients changed significantly; the lowest number was 12,591, and the maximum was 19,863. By examining these mutations, we identified the mutated genes that were common to all patients.ConclusionsIn this study, the highest mutation rates were detected in the PRIM2 and MAP2K3 genes. These genes have not previously been associated with biliary atresia.

Biliary Atresia Splenic Malformation Syndrome: A Single Center Experience

Abstract:&#x0D; Introduction: The cause of biliary atresia (BA) is not understood exactly as well as biliary atresia splenic malformation (BASM) syndrome. BA is destructive biliary fibrosis; the etiology may be multifactorial. Association of cytomegalovirus (CMV) and BA have been shown in many reports but CMV and BASM have not been mentioned in the literature. So we aimed to report BASM experiences, an association of CMV infection and need of duodenoduodenostomy if preduodenal portal vein exists.&#x0D; Materials and Methods: The data were collected retrospectively from Cukurova University which is one of the largest tertiary hospitals in Turkey between 2005-2017. The patients of sex, age, blood chemistry counts, TORCH infections blood parameters, BA types, operational findings and mortality were noted.&#x0D; Results: In total, 59 BA patients were diagnosed between 2005- 2017. Seven of them were classified as BASM. The median age of them was 60 days (45-90 days). Three of them were girl and 4 of them were male in gender. The main complaint of whole patients was jaundice. The jaundice of 6 patients began since birth. One of them began at 20 days-age. Median total / direct blood bilirubin levels were 9.6 / 5.4 mg/dl. Median values of liver function tests; ALT, AST and GGT were 77 IU/L, 201 IU/L and 607 IU/L respectively.&#x0D; Five of the patients showed positive results for anti-CMV immunoglobulin M. All had positive anti-CMV Ig G and anti-toxoplasmosis Ig G.&#x0D; Evaluation of the types of BA revealed that one patient had type 2, while all others had type 3. Four of BASM patients had polysplenia and one had asplenia. Five of them had a preduodenal portal vein. All of them had midgut malrotation. One had inferior vena cava interruption. One had hepatic artery anomaly which was originated from SMA.&#x0D; The median time of follow-up was 4 years (1-5 years). All of them are alive and 1 required liver transplantation.&#x0D; Conclusion: BASM should be kept in mind by the surgeon for the requirement of additional surgical procedures such as Ladd procedure, duodenoduodenostomy with Kasai Porto-enterostomy.&#x0D; Duodenoduodenostomy may be performed when the existence of preduodenal portal vein.&#x0D; Further research is recommended for CMV infection and BASM.

Biliary Atresia: Biliary-Enteric Drainage or Primary Liver Transplant?

The paper from LeeVan et al entitled "Biliary-Enteric Drainage vs Primary Liver Transplant as Initial Treatment for Children with Biliary Atresia" is a retrospective cohort study that examines long-term outcomes for children with biliary atresia (BA) through analysis of information obtained from the California Office of Statewide Health Planning and Development (OSHPD), an administrative database. Specifically, the authors compare outcomes between a cohort of BA patients who underwent a biliary enteric drainage (BED) procedure (presumably a Kasai hepatoportoenterostomy) as the primary therapy to those who underwent a primary liver transplant (pLT) without a previous BED.

Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia

BackgroundGlypican-3 plays a vital role in regulating embryonic morphogenesis of the liver. This study aimed to investigate associations of hepatic expressions of glypican-3 and alpha-smooth muscle actin with clinical parameters in biliary atresia. MethodsLiver specimens were obtained from 20 biliary atresia infants and 7 non-biliary atresia controls. Relative mRNA expressions of glypican-3, alpha-smooth muscle actin, and signaling molecules of Wnt/β-catenin were measured using real-time polymerase chain reaction. Protein expressions of glypican-3 and alpha-smooth muscle actin were examined using immunohistochemistry. Masson’s trichrome staining was conducted to evaluate the stage of liver fibrosis. ResultsUp-regulation of glypican-3 mRNA expression was observed in biliary atresia livers, and its expression was positively associated with alpha-smooth muscle actin, β-catenin, c-Myc, and cyclin D-1. Immunostaining scores of glypican-3 and alpha-smooth muscle actin were significantly increased in biliary atresia livers. Biliary atresia patients with poor outcomes had significantly greater glypican-3 expression than those with good outcomes, consistent with hepatic alpha-smooth muscle actin expression analysis. Hepatic glypican-3 expression was associated with age, albumin, aspartate transaminase, and alkaline phosphatase in biliary atresia patients, while hepatic alpha-smooth muscle actin expression was correlated with alkaline phosphatase in the patients. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers. There was a positive relationship between glypican-3 and alpha-smooth muscle actin expression in biliary atresia livers. Combined high expressions of glypican-3 and alpha-smooth muscle actin were associated with poor survival. ConclusionHepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia.

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

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.

Bilirubin level 1 week after hepatoportoenterostomy predicts native liver survival in biliary atresia.

To determine a very early predictive biomarker after hepatoportoenterostomy (HPE) for the prediction of native liver survival in biliary atresia (BA) patients. A retrospective chart review was conducted of BA patients in our hospital between August 2000 and April 2019. The serum total bilirubin (T-bil), direct bilirubin, and gamma-glutamyl transferase level 1 week after HPE were analyzed. The clinical outcome predictors were investigated. A total of 90 BA patients were recruited. Receiver operating characteristic curve analysis showed that a post-HPE 1-week T-bil level ≤4.85 mg/dL predicted jaundice-free after HPE (P = 0.02). BA patients with a post-HPE 1-week T-bil ≤4.85 mg/dL were more likely to be jaundice-free within 3 months of HPE (odds ratio = 3.53; P = 0.006). Kaplan-Meier plot analysis showed that the likelihood of native liver survival and jaundice-free native liver survival were significantly higher in BA subjects with a post-HPE 1-week T-bil ≤4.85 mg/dL than in other subjects (P = 0.01 and 0.01, respectively). The serum post-HPE 1-week T-bil level may predict the long-term outcome in BA patients. A post-HPE 1-week T-bil ≤4.85 mg/dL correlated with better native liver survival and jaundice-free native liver survival in BA patients.

Correlation of Interleukin-33/ST2 Receptor and Liver Fibrosis Progression in Biliary Atresia Patients.

Background/Aims: Biliary Atresia (BA) is a devastating pediatric liver disease and characterized by aggressive liver fibrosis progression. The Interleukin-33 (IL-33)/ST2 receptor signaling axis has been demonstrated to be involved in several autoimmune and liver diseases. Since immune dysregulation is a contributor to BA pathogenesis, we aimed to investigate the role of IL-33/ST2 receptor in the progression of liver fibrosis in BA patients.Materials and Methods: The study included 36 BA patients (18 good- and 18 poor-prognosis BA patients); and 8 cholestasis infants as the control group. Patients' information and clinical data were retrospectively collected and compared. Liver fibrosis stage was determined by Masson's trichrome staining. Gene expression levels of IL-33, ST2 receptor, and TFG-β1 were detected by quantitative real-time PCR. MC count, IL-33, TGF-β1, and Interleukin-13 (IL-13) expressions were evaluated by immunohistochemistry. Serum IL-33 expression level was detected by enzyme-linked immunosorbent assay. Co-expression of MC and ST2 receptor was detected by immunofluorescence. In vitro mast cell was cultured with IL-33 stimulation, and ST2 receptor and TGF-β1 expressions were detected.Results: Compared with cholestasis control, BA patients had significantly higher GGT level and Masson score. Expression levels of IL-33, TGF-β1, and IL-13 were significantly increased in BA patients compared to control group, especially in poor-prognosis BA patients. Co-expression of ST2 receptor and MC was found in BA liver tissues. The MC count was markedly higher in BA patients especially in poor-prognosis subgroup. Serum IL-33 level was significantly elevated in poor-prognosis BA patients and related to a higher Masson score. In vitro mast cell culture exhibited significant upregulation of ST2 receptor and TGF-β1 mRNA expression after IL-33 stimulation.Conclusions: IL-33/ST2 receptor signaling axis is correlated with liver fibrosis progression in BA patients, and mast cells participates in this process. These indicate potential prognostic evaluation factors for BA patients and can help in the postoperative management to achieve better long-term prognosis in BA patients.

Management of Biliary Atresia in France 1986 to 2015: Long-term Results.

This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available. The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed. A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 μmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001). In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT.