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Background: In patients with biliary atresia (BA), severe portal hypertension (HTN) develops even with successful bile flow restoration, suggesting an intrinsic factor driving portal HTN independent from bile obstruction. We hypothesize that patients with BA have abnormal portal vein (PV) development, leading to PV hypoplasia., Methods: In this observational cohort study, we enrolled patients who were referred to a tertiary center from 2017 to 2021 to rule out BA. Newborns who underwent computed tomography angiogram as a clinical routine before intraoperative cholangiogram, and laparoscopic Kasai hepatoportoenterostomy. The diameter of the PV and hepatic artery (HA) were compared to the degree of liver fibrosis in the wedge biopsies. The jaundice clearance, native liver survival, and clinical portal hypertensive events, including ascites development and intestinal bleeding, were assessed., Results: 47 newborns with cholestasis were included in the cohort; 35 were diagnosed with BA. The patients with BA had a smaller median PV diameter (4.3 vs. 5.1 mm; p < 0.001) and larger median HA diameter (1.4 vs. 1.2 mm; p < 0.05) compared to the patients with other forms of cholestasis. The median PV and HA diameter did not correlate with the degree of liver fibrosis. Among 35 patients with BA, 29 patients (82.9%) achieved jaundice clearance, and 23 patients (65.7%) were alive with their native liver at two years of age. Seven patients (20%) developed intestinal bleeding, and seven patients (20%) developed ascites, with one overlapping patient., Conclusion: PV hypoplasia is present in patients with BA independent of liver fibrosis at the time of diagnosis., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Prenatally diagnosed hepatic hilar cysts are a challenging finding for the clinician. They can either be a sign of cystic biliary atresia (BA) or a choledochal cyst (CC), two diagnoses with different postnatal management and prognosis. Based on a case report of four patients, we aim to propose a management algorithm for prenatally diagnosed "hepatic hilar cysts"., Case Presentation: A hepatic hilar cyst, ranging from 5 to 25 mm, was detected prenatally in all four girls confirmed postnatally along with the presence of a gallbladder. Stool color was normal until two weeks of life at which time the stool color became lighter, and the patients developed cholestasis. All were operated before seven weeks of life: Case 1 had a CC with patent but irregular intrahepatic bile ducts at intraoperative cholangiogram, and no communication with the duodenum. A Roux-en-Y bilioenteric anastomosis was performed. The cyst showed complete epithelial lining loss, and liver pathology showed BA features. Case 2 had the final diagnosis of cystic BA with patent but abnormal intrahepatic bile ducts. She underwent two operations: the first operation at four weeks as described for case 1, since intraoperative findings were similar, as was histology. As cholestasis increased postoperatively, she underwent a Kasai hepato-porto-enterostomy six weeks later, where distinct BA findings were found with complete scarring of the hilar plate. Case 3 had a cystic BA with the cyst located within the common bile duct and atretic bile ducts proximal to the porta hepatis. It exhibited no communication with the liver or duodenum. A Kasai operation was performed, with histology showing complete epithelial loss within the cyst wall and scarring of the hilar plate. Case 4 had a cystic BA presenting a completely obliterated hepatic duct with the cyst lying within the common bile duct. A Kasai procedure was performed. Histology showed a common bile duct with a residual lumen of 0.1 mm., Conclusions: The spectrum of disease from CC to BA in the setting of a prenatally discovered hepatic hilar cyst is emphasized. Even if cholangiogram differentiates most patients with BA from those with CC, caution is advised for transitional types., (© 2024. The Author(s).)

Biliary atresia (BA) is a congenital disease that occurs when extrahepatic bile ducts are either absent or deficient, resulting in liver fibrosis, portal hypertension, and eventually cirrhosis. It is the most common cause of persistent obstructive jaundice in newborns lasting more than two weeks is this condition. Abdominal ultrasound (US) is the primary imaging technique used to diagnose BA, while computed tomography (CT) is reserved for more complex cases. The gold standard for diagnosing BA is still intraoperative cholangiogram with liver biopsy. Treatment for BA usually involves Kasai hepatoportoenterostomy, but some patients still require liver transplantation due to diagnostic delays and advanced disease. In this study, the authors present the case of a 3-month-old infant with biliary atresia and its ultrasound characteristics, who underwent liver transplantation due to advanced disease. The primary objective of imaging is to provide a prompt diagnosis, given the crucial significance of timely surgical intervention., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Purpose: Early diagnosis of biliary atresia (BA) is critical for best outcomes, but is challenged by overlapping clinical manifestations with other causes of obstructive jaundice in neonates. We evaluate the performance of the modified Simple BA Scoring System (SBASS) in diagnosing BA., Methods: We performed a prospective, cross-sectional study on infants with cholestatic jaundice (June 2021-December 2022). Modified SBASS scoring was applied and compared to the eventual diagnosis (as per intraoperative cholangiogram (IOC) and liver histopathology). The score (0-6), consists of gall bladder length < 1.6 cm (+ 1), presence of triangular cord sign (+ 1), conjugated bilirubin:total bilirubin ratio > 0.7(+ 2), gamma-glutamyl transferase (GGT) ≥ 200 U/L (+ 2)., Results: 73 were included: Fifty-two (71%) had BA. In the non-BA group, 6 (28%) had percutaneous cholangiography (PTC) while 15 (72%) had intraoperative cholangiogram (IOC). At a cut-off of 3, the modified SBASS showed sensitivity of 96.2%, specificity of 61.9% and overall accuracy of 86.3% in diagnosing BA. Area under receiver operating characteristic curve was 0.901. GGT had the highest sensitivity (94.2%), while triangular cord sign showed the highest specificity at 95.2%., Conclusion: The SBASS provides a bedside, non-invasive scoring system for exclusion of BA in infantile cholestatic jaundice and reduces the likelihood of negative surgical explorations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients., Methods: This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design., Results: The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively)., Conclusion: The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: This study systematically reviewed our team's research on the mechanism and assessment of liver fibrosis in BA, summarized our experience, and discussed the future development direction., Methods: In this study, Pubmed and Wanfang databases were searched to collect the literature published by our team on the mechanisms of liver fibrosis in BA and the assessment of liver fibrosis in BA, and the above research results were systematically reviewed., Results: A total of 58 articles were retrieved. Among the included articles, 25 articles related to the mechanism of liver fibrosis in BA, and five articles evaluated liver fibrosis in BA. This article introduces the key pathways and molecules of liver fibrosis in BA and proposes a new grading system for liver fibrosis in BA., Conclusions: The new BA liver fibrosis grading method is expected to assess children's conditions, guide treatment, and improve prognosis more accurately. In addition, we believe that the TGF-β1 signaling pathway is the most important in the study of liver fibrosis in BA, and at the same time, the study of EMT occurrence in BA should also be deepened to resolve the controversy on this issue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The prognostic factors of subsequent liver transplantation (LT) in patients with biliary atresia (BA) who presented with jaundice-free native liver survival were investigated., Methods: This study retrospectively reviewed patients who underwent portoenterostomy (PE) for BA. Patients with jaundice-free native liver survival at 1 year postoperatively were divided into the autologous liver survivor and liver transplant recipient groups. Peri- and postoperative data were compared between the two groups., Results: Among 97 patients with BA, 29 who received LT within 1 year after PE were excluded from the analysis. Further, 48 patients currently living with native liver and 20 who received LT after 1 year postoperatively were compared. Bile lake (BL) was the strongest risk factor of LT. The risk score was 2.38 ∗ B L s c o r e + 0.00466 ∗ T B A , and the area under the receiver operating characteristic curve was 0.83. Patients with BL and those without significantly differed in terms of the native liver survival rate. Patients with BL who presented with not only cholangitis but also gastrointestinal hemorrhage and hepatopulmonary syndrome received LT., Conclusion: BL can cause different pathologies. Moreover, it is an evident risk factor of subsequent LT in patients with BA who are living with native liver at 1 year after PE., (© 2024. The Author(s).)

Purpose: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE)., Methods: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve., Results: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75)., Conclusions: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up., Level of Evidence: Level III., (© 2024. The Author(s).)

Purpose: Frequent post-operative cholangitis in biliary atresia (BA) affects the long-term native liver survival. This study assessed the characteristics of early cholangitis and their influence on the prognosis., Methods: Forty-three patients with BA who underwent surgery between 2000 and 2020 were analyzed for routine inflammatory markers. Early cholangitis characteristics were compared between native liver survivor (NLS) and living donor liver transplant (LDLT) patients., Results: Among the 43 patients, 30 (69.8%) experienced 130 episodes of cholangitis. In the area under the receiver operating characteristics curve (AUROC) analysis, the cutoff value of the total cholangitis episodes was 3, with an area under the AUROC curve of 0.695 (95% confidence interval 0.522-0.868). Before 3 years old, 113 episodes (86.9%) of cholangitis were observed. The white blood cell, C-reactive protein, and alanine aminotransferase values at cholangitis onset did not markedly differ between the LDLT and NLS groups. Conversely, the neutrophil-to-lymphocyte ratio in the NLS group was significantly lower than in the LDLT group (0.85 vs. 1.63, p < 0.001)., Conclusions: Cholangitis in the NLS group was lymphocyte-dominant and atypical in its pathogenesis. Lymphocyte-dominant cholangitis is non-suppurative, and future research should clarify its pathogenesis to improve the treatment and prognosis of BA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000-20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50-75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60-75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes., (© 2024. Springer Nature Limited.)

Hereditary angioedema is a potentially life-threatening autosomal dominant condition, causing attacks of angioedema due to failure to regulate bradykinin. Nearly all cases of hereditary angioedema are caused by mutations in the gene encoding C1 inhibitor, SERPING1 . C1 inhibitor is a multifunctional protein produced in the liver that regulates the kallikrein-kinin system at multiple points. An infant with genetically confirmed hereditary angioedema and low C1 inhibitor levels (but without previous episodes of angioedema) underwent liver transplantation for biliary atresia, an unrelated condition. Liver transplantation led to normalization of the C1 inhibitor level and function. To our knowledge, this represents the first patient to be potentially cured of hereditary angioedema., (Copyright © 2024 Massachusetts Medical Society.)

Background: Biliary atresia is the most common cause of obstructive jaundice in infants and conventional cholangiography is the current diagnostic gold standard. Fluorescent cholangiography with indocyanine green can enhance biliary tree visualization during surgery because it is exclusively excreted into the bile ducts and eventually into the intestine. Therefore, we hypothesized that indocyanine green presence in stool could confirm bile duct patency in infants., Methods: A prospective single center cohort study was performed on infants (age ≤ 12 months) with and without jaundice after obtaining IRB approval. Indocyanine green was administered intravenously (0.1 mg/kg). Soiled diapers collected post-injection were imaged for fluorescence., Results: After indocyanine green administration, fluorescence was detected in soiled diapers for control patients (n = 4, x = 14 h22 m post-injection) and jaundiced patients without biliary atresia (n = 11, x = 13 h28 m post-injection). For biliary atresia patients (n = 7), post-injection soiled diapers before and after Kasai portoenterostomy were collected. Fluorescence was not detected in stool from 6 of 7 biliary atresia patients. As a test, indocyanine green detection in stool was 97% accurate for assessing biliary patency., Conclusion: Fluorescent Imaging for Indocyanine Green (FIInd Green) in stool is a fast and accurate approach to assess biliary patency non-invasively in infants., Level of Evidence: Level III., Competing Interests: Conflicts of interest The authors have no conflicts of interests to declare and no financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Acute-on-chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse., Method: We performed a retrospective analysis of patients with BA aged <18 years who underwent LT between 2011 and 2021 at our institution. ACLF was defined using the pediatric ACLF criteria: ≥1 extra-hepatic organ failure in children with decompensated cirrhosis., Results: Of 107 patients (65% female; median age 14 [9-31] months) who received a LT, 13 (12%) had ACLF during the index admission prior to LT. Two (15%) had Grade 1; 4 (30%) had Grade 2; and 7 (55%) had Grade ≥3 ACLF. ACLF cohort was younger at time of listing (5 [4-8] vs. 9 [6-24] months; p < .001) and at LT (8 [8-11] vs. 16 [10-40] months, p < .001) compared to no-ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20-53] vs. 10 [6-19] mL/kg; p < .001) and blood transfusion requirements (33 [21-69] vs. 18 [7-25] mL/kg; p = .004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p = .04) and had higher total hospital length of stay (106 [45-151] vs. 13 [7-30] days; p = .023). Rate of return to the operating room, hospital readmission rates, and 1-year post-LT survival rates were comparable between the groups., Conclusion: Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT., (© 2024 Wiley Periodicals LLC.)

Background: Bile atresia is children's leading cause of cirrhosis. Its high morbidity and mortality are explained by its complications, including gastrointestinal bleeding and portal hypertension. Umbilical hernia has been embryologically and clinically associated with portal hypertension and cirrhosis; however, the clinical evolution of patients with bile atresia and umbilical hernia is unknown, so the aim of the study is to describe this link., Objective: To determine the prevalence of the coexistence of AVB and HU in patients in a tertiary hospital, and describe the clinical evolution of these patients with respect to the presence/absence of HU as a strategy in the search for prognostic factors of morbidity and mortality., Material and Methods: This is an observational, descriptive, retrospective, and longitudinal study that included patients with bile atresia in a tertiary pediatric hospital. The variables related to bile atresia were analyzed, and the clinical evolution was described according to the presence or absence of UH., Results: 56 patients with bile atresia were included, of which 69.6% were females. Portal hypertension occurred in 80.4%, with the presence of collateral venous network, gastrointestinal bleeding, ascites, and hepatomegaly being the indirect clinical data most often presented. The frequency of coexistence of umbilical hernia and bile atresia was 75%. Portal hypertension, collateral venous network, gastrointestinal bleeding, ascites, and small esophageal varices were the significantly more prevalent variables in patients with umbilical hernia., Conclusions: Patients with bile atresia have a greater possibility of developing umbilical hernia and that it is associated with a more advanced evolution of portal hypertension and its associated signs and complications., (Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.)

Objectives: To holistically evaluate neurodevelopmental outcomes and quality of life (QOL) of Japanese patients with biliary atresia (BA) and to investigate the factors associated with the outcomes., Methods: This study enrolled patients with BA aged 5-18 years who visited Osaka University Hospital in 2021. Neurodevelopmental assessments were performed to evaluate intellectual ability, cognitive functions and adaptive skill levels. Furthermore, emotional and behavioral issues, characteristics of attention deficit hyperactivity disorder, and QOL were concomitantly assessed in the same cohort. Biochemical and social factors associated with the results were examined., Results: Fifty-three patients, with a median age of 11.2 years were included in the analyses. Patients with BA had a significantly lower Full-Scale Intelligence Quotient or developmental quotient (FSIQ/DQ) score and Vineland Adaptive Behavior Scale (VABS) composite score than the general Japanese population. Household education level and short stature were associated with low and borderline FSIQ/DQ and VABS composite scores, respectively. Among patients with low and borderline FSIQ/DQ scores, those with average or high VABS composite scores received significantly less neuroeducational care than those with low and borderline VABS composite scores. Despite the low FSIQ/DQ and VABS composite scores, the total QOL scores were higher than those of the general population., Conclusion: Patients with BA had intellectual and behavioral impairments. Notably, patients with intellectual impairments are overlooked and not followed up, especially if adaptive skills are maintained., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histologic findings in patients after LDLT for biliary atresia., Methods: Patients aged <19 years who underwent LDLT for biliary atresia at our institution and followed up for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathologic findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathologic fibrosis scores and PV stenosis findings., Results: The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 cut-off index (COI) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (P = .016) and F1 (P = .012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n = 5) and 0.72 COI in patients without PV complications (n = 51) (P = .0001)., Conclusion: M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children., Methods: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography., Results: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002)., Conclusion: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis., Methods: There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute., Results: There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001)., Conclusions: The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients., Impact: What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1-191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA., (© 2023. The Author(s).)

Objective: Biliary atresia (BA) is a progressive fibro-obliterative disease of the biliary tract, which results in end-stage liver disease. However, liver fibrosis progression may continue even after Kasai surgery. Recent evidence showed that collagen plays a pivotal role in the progression of liver fibrosis in BA. However, most studies were conducted in developed countries. We investigated the expressions of the collagen gene cluster (COL6A1, COL6A2, COL6A3, and COL1A1) in BA patients in Indonesia., Results: There was a significant down-regulated expression of COL6A1 (ΔC T 9.06 ± 2.64 vs. 5.42 ± 2.41; p = 0.0009), COL6A2 (ΔC T 8.25 ± 2.07 vs. 5.77 ± 3.51; p = 0.02), COL6A3 (ΔC T 11.2 ± 6.08 vs. 6.78 ± 3.51; p = 0.024), and COL1A1 (ΔC T 3.26 ± 1.71 vs. 0.19 ± 2.76; p = 0.0015) in BA patients compared to controls. Interestingly, the collagen gene cluster expressions were significantly associated with the presence of cirrhosis (p = 0.0085, 0.04, and 0.0283 for COL6A1, COL6A2, and COL6A3, respectively). In conclusion, our study shows the changes in the collagen gene cluster, particularly collagen type I and VI, expressions in patients with BA in a particular developing country. Our findings suggest the role of these collagen gene clusters in the liver fibrogenesis of BA., (© 2023. The Author(s).)

Abstract: The application of intracavity contrast-enhanced ultrasound in the evaluation of biliary disease has been confirmed valuable among pediatric population. This pictorial essay aims to demonstrate the role of percutaneous ultrasound cholangiography (PUSC) with microbubbles in the diagnosis of different pediatric biliary diseases in our center. The biliary system's morphologic characteristics in PUSC mode of neonatal hepatitis, biliary atresia, choledochal cysts, and biliary complications of hepatobiliary surgery are presented., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Recent studies demonstrate the success of Kasai portoenterostomy for biliary atresia (BA) is linearly related to infant age at time of Kasai. We sought to review the feasibility and safety of laparoscopic needle micropuncture cholangiogram with concurrent core liver biopsy (if needed) for expedited exclusion of BA in patients with direct conjugated hyperbilirubinemia., Methods: Expedited laparoscopic cholangiogram and liver biopsy were instituted at our facility for infants with direct hyperbilirubinemia for whom clinical exam and laboratory workup failed to diagnose. A retrospective chart review was performed in infants <1 year with hyperbilirubinemia from 2016 to 2021. Demographics, preoperative evaluation, procedure details, and complications were reviewed., Results: Two hundred ninety-seven infants with unspecified jaundice were identified, of which, 86 (29%) required liver biopsy. Forty-seven percutaneous liver biopsies were obtained including 8 (17%) in whom BA could not be excluded. Laparoscopic cholangiogram was attempted in 47 infants following basic workup; BA was diagnosed in 22 infants (47%) of which 3 were <18 days old. Biliary patency was demonstrated laparoscopically in 22 of 25 (88%); 3 (12%) required conversion to open cholangiogram. Infants with percutaneous liver biopsy had an average delay of 3 days (range: 2-36) to cholangiogram. Preoperative studies and liver biopsy alone did not reliably exclude the diagnosis of BA., Conclusion: Laparoscopic cholangiogram with liver biopsy is a safe procedure resulting in the confirmation or exclusion of BA in infants. Forty-seven percent of infants who underwent laparoscopic cholangiogram were found to have BA; those who were surgical candidates underwent Kasai during the same operation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Two-dimensional shear wave elastography (2D-SWE) has been proposed for detecting liver fibrosis in biliary atresia., Objectives: To assess the performance of 2D-SWE for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia., Materials and Methods: Five electronic databases were searched to identify studies investigating the performance of 2D-SWE for diagnosing liver fibrosis in biliary atresia in children. We constructed the summary receiver operating characteristic (SROC) curves of 2D-SWE for detecting advanced liver fibrosis and cirrhosis, and then calculated the area under the SROC curves (AUROCs)., Results: Six studies with 470 patients (ages 55 days to 6.6 years) were included. The median correlation coefficient of 2D-SWE with pathological liver fibrosis stages was 0.779 (range: 0.443‒0.813). The summary AUROCs for advanced liver fibrosis and cirrhosis were 0.929 and 0.883, respectively. The summary sensitivity and specificity of 2D-SWE for advanced liver fibrosis were 88% (95% confidence interval [CI]: 80‒94%) and 85% (95% CI: 77‒91%) with I values of 0% and 45.6%, respectively, and for cirrhosis were 80% (95% CI: 72‒87%) and 82% (95% CI: 77‒86%) with I values of 12.9% and 0%, respectively. The diagnostic odds ratio (DOR) of 2D-SWE for advanced liver fibrosis and cirrhosis were 40.3 (95% CI: 18.2‒89.4) and 18.9 (95% CI: 11.2‒31.7), respectively. For preoperative detection of cirrhosis, the pooled AUROC, sensitivity, specificity, and DOR based on the four 2D-SWE studies were 0.877, 79% (95% CI: 71‒86%), 82% (95% CI: 77‒86%), and 17.58 (95% CI: 10.35‒29.85), respectively., Conclusions: Results show that 2D-SWE has potential as a non-invasive tool for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis., Materials and Methods: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM., Results: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up., Conclusions: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: A connection between the bowel and bile ducts after the Kasai hepatoportoenterostomy (HPE) procedure poses a risk of ascending cholangitis. There were only a few evidence-based consensuses on the benefits of prophylactic antibiotics. This study aims to assess the value of prophylactic antibiotics in reducing the risk of cholangitis following the Kasai HPE procedure., Methods: Meta-analysis is performed using random-effects model from the search result of 5 online databases (PubMed, Google Scholar, EBSCO MEDLINE, ClinicalTrials.gov , and EuropePMC) from inception to October 27, 2021. The keywords used were "antibiotic," "antimicrobial," "Kasai," "portoenterostomy," "biliary atresia," and "bile duct atresia." Cochrane Risk of Bias tool and Newcastle-Ottawa Scale is used to assess the risk of bias. The outcomes are incidence of cholangitis and native liver survival., Results: Six studies consisting of 4 cohorts and 2 cross-sectional studies were extracted. A total of 714 patients reported different cholangitis incidence after prophylactic antibiotics administration post-Kasai HPE. The incidence of cholangitis following Kasai HPE was not statistically significant among participants. There is conflicting evidence on the efficacy of antibiotics in prolonging native liver survival., Conclusions: The existing evidence does not support the administration of prophylactic antibiotics in preventing cholangitis after Kasai HPE among biliary atresia patients. Additionally, their roles in native liver survival are still inconclusive. The fact that there were heterogeneous method and antibiotic usage between existing studies must also be highlighted for better design in future studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation., Methods: Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses., Results: Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA., Conclusion: A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC., (© 2023. The Author(s).)

Roux-en-Y cholangiojejunostomy is a standard procedure for biliary reconstruction in pediatric living donor liver transplantation (LDLT). However, there is uncertainty on whether the adult standard of Roux branch limb is suitable for pediatric LDLT and its impact on postoperative biliary complications (BC). This study aimed to explore the effect of the short Roux limb and standard limb on pediatric LDLT biliary reconstruction. According to the length of the Roux limb, 168 LDLT children were divided into the routine limb group (n = 108) and the short limb group (n = 60). The incidences of postoperative biliary tract complications between the 2 groups were compared retrospectively. The mean Roux limb length in the short limb group was significantly shorter than that in the routine limb group group (P < .01). There were significant differences in age, height, and weight between the 2 groups (P < .01). However, there were no significant differences in graft-to-recipient weight ratio, intraoperative blood loss, cold ischemia time, and operation time between the 2 groups (P > .01). Moreover, postoperative BC, including refluxing cholangitis, were similar between the 2 groups (P = .876). Furthermore, the history of Kasai surgery, the history of postoperative RC of Kasai, and whether or not the Roux limb was reconstructed had no significant effect on the occurrence of postoperative RC. There was no significant difference in postoperative BC between the short limb and the routine limb in children with living donor liver transplantation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic cholestasis is an age-old problem., Objectives: To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders., Materials and Methods: This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases., Results: This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy., Conclusion: BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10 -11 ). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3 . Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10 -4 ), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

The fetus of a 30-year-old pregnant Japanese woman was diagnosed with absence of inferior vena cava (IVC) and azygos continuation of interrupted IVC without cardiac anomalies at 34 weeks of gestation, and a healthy male neonate weighing 2,910 g was delivered at 37 weeks of gestation. On day 42 after birth, direct bilirubin predominant hyperbilirubinemia and high serum gamma-GTP levels were detected. Computed tomography revealed the presence of a lobulated and accessory spleen, and laparotomy demonstrated type III biliary atresia (BA), confirming the final diagnosis of BA splenic malformation (BASM) syndrome. In retrospect, non-visualization of the gallbladder was missed in utero. The combination of the absence of IVC and BA without cardiac anomalies is far less likely to occur in left isomerism. Although BA remains difficult to detect in utero, special attention should be paid to cases of BA associated with findings of left isomerism, including the absence of IVC, to enable early diagnosis and treatment of BASM.

Background and Aim: Portal hypertension determines the outcome of children with biliary atresia (BA) and is common even after a successful Kasai portoenterostomy (KPE). However, there are no clear-cut guidelines on the age of starting surveillance and the modality (endoscopy vs non-invasive tests [NITs]). In this cohort study, we analyzed our database to find out the utility of NITs in detecting high-risk esophageal varices in BA., Methods: From June 2010 to May 2022, consecutive children of BA who underwent upper gastrointestinal (UGI) endoscopy were included. Esophageal varices were classified as high-risk (grade II with red-color signs or grade III or IV irrespective of red-color signs. NITs such as splenomegaly (clinical and USG), platelet count, aspartate transaminase to platelet ratio index (APRI), and platelet-to-spleen diameter ratio were compared between cases with high-risk and low-risk varices., Results: A total of 110 children, 75 boys (66 successful KPE and 44 failed/KPE not performed) were enrolled. The median age at KPE was 85 days (IQR 63-98). Thirteen (11.8%) children presented with UGI bleeding. The first endoscopy revealed gastroesophageal varices in 75.4% of cases, and 32% of them had high-risk varices. Multivariate analysis revealed failed KPE, history of UGI bleeding, bigger spleen size (> 3.5 cm), lower platelet count (< 150 000), and higher APRI (> 2) are independent predictors of the presence of high-risk esophageal varices., Conclusion: Endoscopy is the best in predicting the presence of high-risk varices that might bleed; hence, early surveillance endoscopy should be started in children with splenomegaly, thrombocytopenia, and high APRI score to prevent variceal bleeding., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes., Methods: One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival., Results: Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome., Conclusion: Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome., Competing Interests: None

Context.—: Biliary atresia (BA) patients can have portal vein (PV) abnormalities., Objective.—: To investigate the explant pathology of BA patients transplanted in adulthood with a focus on portal venous abnormalities., Design.—: Adult BA liver explants were reviewed, along with prior biopsies, Kasai portoenterostomy (KP), and relevant medical records., Results.—: Three explants were identified; all patients were female, with age at diagnosis, KP, and liver transplantation (LT) as follows: (1) less than 1 week, 8 days, and 25 years; (2) 15 weeks, 16 weeks, and 32 years; and (3) 7 weeks, 8 weeks, and 33 years, respectively, with normalization of conjugated bilirubin within 6 months of KP and development of portal hypertension (PHTN) within 3 years of KP for all 3. The first 2 had recurrent cholangitis. Duration of pre-LT PHTN was 22, 29, and 30 years, and that of pre-LT cholangitis was 9, 3, and 0 years, respectively. All 3 explants showed hilar and extrahepatic fibromyxoid intimal hyperplasia of the PV with parenchymal hepatoportal sclerosis. Cholestasis was limited to those with a history of cholangitis. Patient 3, without cholangitis, showed delicate septal fibrosis with peripheral accentuation without biliary cirrhosis., Conclusions.—: In the context of a functioning KP, cholestasis and biliary cirrhosis are likely related to recurrent cholangitis, which may or may not occur after KP. In the absence of biliary cirrhosis, PHTN may be secondary to obliterative venopathy. Adult BA explants should be sampled thoroughly, with a focus on hilar/perihilar connective tissue to include PV branches. Explants may not show biliary cirrhosis and should be reported with appropriate clinicopathologic correlation., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2023 College of American Pathologists.)

Background: Controversies in management of biliary atresia (BA) after hepatoportoenterostomy (HPE) lead to variable treatment protocols. We implemented standardized medical management after HPE, customizing the use of antibiotics and corticosteroids based on patient-specific factors., Methods: In this retrospective analysis, 20 consecutive infants underwent HPE for BA and were compared to a historical cohort. Analysis of successful biliary drainage 3 months after HPE (defined as serum total bilirubin <2 mg/dL) was the primary endpoint; survival with native liver at 2 years was the secondary endpoint., Results: Sixteen of 20 (80%) infants had successful bile drainage, compared to 8 of 20 (40%) infants in the historical cohort (P = 0.0225). Sixteen of 20 patients in the new protocol have reached 2 years of age or required liver transplantation. Among the sixteen, 11 (68.8%) are alive with native livers versus 10 of 20 (50%) in the historical cohort (P = 0.0970)., Conclusion: This preliminary report suggests the potential benefit of tailored use of postoperative antibiotics and corticosteroids in improving biliary drainage after HPE., Level of Evidence: III., (Copyright © 2022. Published by Elsevier Inc.)

Multiple causes of congenital neonatal cholestasis have been identified, and are classified as extrahepatic or intrahepatic. Biliary atresia (BA), Alagille syndrome (AGS), and progressive familial intrahepatic cholestasis (PFIC) are the most common of these. Many factors associated with cholestatic diseases are known to degrade the oral health of these children. What are the oral manifestations associated with these diseases in the pediatric population? The aim of this article was to evaluate the impact of congenital cholestasis on oral health in pediatric patients. A systematic review of case reports and case series was carried out in PubMed, the Cochrane Library, and the Web of Science to identify relevant articles in French and English published up to April 2022. The review included 19 studies, 16 case reports, and three case series. Only studies dealing with BA and AGS were found. These studies showed an impact on jaw morphology, dental structure, and periodontal health. The facial dysmorphism observed in AGS was specific. Exposure to high levels of bilirubin during the period of dental calcification led to particular coloration. Regarding periodontal status, gingival inflammation was common in these patients, probably resulting from the use of certain treatment-associated drugs and poor oral hygiene. Cohort studies are needed to confirm the classification of these children as being at high individual risk of caries. Many major oral manifestations are found in children with AGS and BA, confirming the need to include a dentist in the care team of patients with congenital cholestatic disease as early as possible. It appears necessary to carry out individual prospective studies of each phenotype in order to confirm and better describe the oral impact of these cholestatic diseases and provide adequate medical care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Living donor liver transplantation (LT) is the main treatment for paediatric biliary atresia (BA) in Asia. During LT, a series of haemodynamic changes often occur during LT reperfusion, which is called postreperfusion syndrome (PRS), and PRS is related to a prolonged postoperative hospital stay, delayed recovery of graft function and increased mortality. To reduce adverse reactions after paediatric living donor LT (LDLT), our study's objectives were to ascertain the incidence of PRS and analyse possible risk factors for PRS., Methods: With the approval of the Ethics Committee of our hospital, the clinical data of 304 paediatric patients who underwent LDLT from January 2020 to December 2021 were analysed retrospectively. According to the presence or absence of PRS, the paediatric patients were divided into the non-PRS group and the PRS group. Independent risk factors of PRS were analysed using logistic regression analysis., Results: PRS occurred in 132 recipients (43.4%). The peak values of AST (816 (507-1625) vs 678 (449-1107), p=0.016) and ALT (675 (415-1402) vs 545 (389-885), p=0.015) during the first 5 days after LDLT in paediatric patients with PRS were significantly higher than those in the non-PRS group. Meanwhile, the paediatric patients in the PRS group had longer intensive care unit stays and hospital stays, as well as lower 1-year survival rates. Graft cold ischaemic time (CIT) ≥90 min (OR (95% CI)=5.205 (3.094 to 8.754)) and a temperature <36°C immediately before reperfusion (OR (95% CI)=2.973 (1.669 to 5.295)) are independent risk factors for PRS., Conclusions: The occurrence of hypothermia (<36.0℃) in children immediately before reperfusion and graft CIT≥90 min are independent risk factors for PRS. PRS was closely related to the postoperative adverse outcomes of paediatric patients., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Biliary atresia (BA) is the most common indication for pediatric liver transplantation, and biliary stricture (BS) remains an Achilles' heel for pediatric living donor liver transplantation (LDLT). We investigated the impact of different ischemia times on BS after LDLT in patients with BA. We retrospectively analyzed patients (<18 y) with BA who underwent LDLT between January 2016 and December 2020. Cases with hepatic artery thrombosis, bile leakage, early BS (<2 wk), and early death (<3 mo) were excluded. In all, 572 cases were included. A total of 26 cases (4.55%, 26/572) developed BS: 25 patients with anastomotic stricture and 1 patient with anastomotic stricture combined with left hepatic duct stricture. In addition, the time to diagnosis of BS ranged from 1.8 to 53.0 months (mean, 13.0 mo and median, 8.2 mo) after transplantation. A multivariate logistic regression analysis showed that arterial ischemia time (AIT), per 10 minutes (OR=1.222, 95% CI: 1.007-1.438, p =0.04) was the only independent risk factor for the development of BS after LDLT in patients with BA. What is more, the 5-year cumulative risk of BS between the AIT ≥40 minutes and AIT <40 minutes groups was 2.79% versus 10.57%. AIT was the only independent risk factor for the development of BS after LDLT with BA, and AIT ≥40 minutes would increase the 5-year cumulative risk of BS in our study. A shorter AIT, especially AIT <40 minutes, should be kept to decrease BS., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Biliary atresia (BA) is a severe cholangiopathy in infants. It is characterized by inflammatory fibro-obliteration of the intra- and extrahepatic bile ducts. Although the restoration of bile flow can be successful after Kasai operation, the rapid progression of liver fibrosis can continue, leading to cirrhosis. It is believed that the progression of liver fibrosis in BA is exacerbated by complicated mechanisms other than the consequence of bile duct obstruction. The fibrogenic cascade in BA liver can be divided into three stages, including liver inflammatory injury, myofibroblast activation, and fibrous scar formation. Recent studies have revealed that the activation of an immune response following bile duct injury plays an important role in promoting the inflammatory process, the releasing of inflammatory cytokines, and the development of fibrogenesis in BA liver. In this article, we summarized the evidence regarding liver inflammatory injury and the possible mechanisms that explain the rapid progression of liver fibrosis in BA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy., Case Presentation: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution., Conclusions: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy., (© 2023. The Author(s).)

Background: The appropriate timing of liver transplantation (LT) in patients with biliary atresia (BA) who survived with their native livers until adolescence remains controversial. The liver-spleen volume ratio (LSR) has been reported to be efficacious in predicting the prognosis of chronic liver disease. We investigated whether LSR could predict long-term native liver prognosis and serve as an indication for LT in patients with BA., Methods: Patients with BA who survived with their native liver until the age of 15 years were included. These patients were classified into 2 groups. The unfavorable prognosis group included patients who underwent or were awaiting LT or developed complications such as refractory cholangitis or gastrointestinal bleeding due to esophagogastric or intestinal varices. The favorable prognosis group included patients who survived with their native liver without complications. We compared the 2 groups regarding LSR, hematological, and histologic data., Results: Of 19 patients, 8 were in the unfavorable prognosis group, and 11 were in the favorable prognosis group. LSR was significantly lower in the unfavorable prognosis group (P = .009). Analysis of the receiver operating characteristic curve showed that the area under the curve of the LSR was 0.891, which was higher than the area under the curve of liver fibrosis markers. The optimal LSR cut-off value for predicting poor native liver prognosis was 1.97, with a sensitivity of 75.0% and a specificity of 87.5%., Conclusions: The LSR reflects splenomegaly and liver atrophy. The LSR might be a reliable predictor of native liver prognosis and could guide decisions about LT in patients with BA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute-on-chronic liver failure (ACLF) occurs in children with biliary atresia (BA) awaiting liver transplantation (LT). However, data on transplant outcomes in ACLF are limited. Our aim was to characterize ACLF and determine its effect on transplant outcome and resource utilization. Using a linkage of the Scientific Registry of Transplant Recipients and Pediatric Health Information System, we identified children with BA between 3 months and 18 years at the time of listing who received a transplant from 2003 to 2018 and were hospitalized while waiting. ACLF was defined by the presence of at least 1 extra-hepatic organ failure during a pre-LT hospitalization. In all, 1044 patients (58% female, median age at listing 7.0 months IQR 5.0-14.0) were included. Thirty-four percent (351/1044) of the patients had at least 1 ACLF hospitalization. Patients with ACLF had longer waitlist times (114 [54-231] vs. 81 [35-181] days, p < 0.001), and were more likely to be listed as Status 1 (8% vs. 4%, p = 0.02). Pre-LT resource utilization was significantly higher in ACLF patients. There were no differences in mortality at 30 days (ACLF 3% vs. No ACLF 2%, p = 0.17), 90 days (ACLF 3% vs. No ACLF 2%, p = 0.24), 1 year (ACLF 3% vs. No ACLF 2%, p =0.23), 3 years (ACLF 4% vs. No ACLF 3%, p = 0.58), or 5 years (ACLF 5% vs. No ACLF 4%, p = 0.38) after LT. ACLF status was not associated with increased post-transplant mortality (adjusted HR 1.51, 95% CI 0.76-3.0, p =0.25). ACLF is an important morbidity in children with BA awaiting LT as it is associated with higher resource utilization and longer waitlist times. Further studies are needed to help understand the spectrum of ACLF and better prioritize critically ill children awaiting LT, as our study shows successful post-LT outcomes in children with BA and ACLF., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Objectives: To evaluate the response and outcome with prolonged intravenous antibiotics including home-based intravenous antibiotics in children with intractable cholangitis (IC) after Kasai portoenterostomy (KPE) for biliary atresia (BA)., Methods: A retrospective review of treatment and outcome of children with IC post KPE (no resolution after four weeks of antibiotics) was done between 2014 and 2020. A protocol-based antibiotic regimen was used based on sensitivity and hospital antibiogram. Children afebrile for more than three days were discharged on home intravenous antibiotics (HIVA)., Results: Twenty children with IC were managed with prolonged antibiotic regimen, including HIVA. All patients were initially listed for liver transplantation (LT) with indication being IC (n = 20) with portal hypertension (n = 12). Seven patients had bile lakes of which four underwent percutaneous transhepatic biliary drainage. Bile culture grew Klebsiella in four and Escherichia coli and Pseudomonas one each. There were eight children with IC who had positive blood culture with most of these organisms being gram-negative (Escherichia coli: 5, Klebsiella pneumoniae: 2, Enterococcus: 1). Median duration of antibiotics was 58 days (interquartile range [IQR] 56-84). Median follow-up period post cholangitis was three years (IQR 2-4). Following treatment, 14 patients were successfully delisted from LT waitlist and are presently jaundice-free. Two of the five patients undergoing LT died of sepsis. One patient died awaiting LT., Conclusion: Timely and aggressive step-up antibiotic regimen may successfully treat IC and prevent/delay LT. HIVA provides a cost-effective and comfortable environment for a child which might improve compliance with intravenous antibiotics., (© 2023. Indian Society of Gastroenterology.)

Background and Aims: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19., Approach and Results: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p <0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p <0.001) also among patients operated <60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004)., Conclusions: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases.)

Background: Children with biliary atresia (BA) may experience various infections (e.g., cholangitis, bacteremia, and viral respiratory infections (VRI)) throughout their disease course. This study aimed to identify and describe these infections and their risk factors for development in children with BA., Methods: This retrospective observational study identified infections in children with BA using predefined criteria, including VRI, bacteremia with and without central line (CL), bacterial peritonitis, positive stool pathogens, urinary tract infections, and cholangitis. Infections were identified until liver transplant, death or last follow-up with native liver. Infection-free survival was estimated by Kaplan-Meier analysis. Logistic regression was used to estimate odds of infection per clinical characteristics. Cluster analysis was performed to identify patterns of infection development., Results: 48 of 65 (73.8%) children had ≥1 infection during their disease course (mean length of follow up: 40.2 months). Cholangitis (n = 30) and VRI (n = 21) were most common. Nearly half (45%) of all infections developed within 3-months of Kasai hepatoportoenterostomy. Kasai performed ≥45 days of life was associated with 3.5-fold increased risk of any infection (95% CI 1.2-11.4). Risk of VRI was inversely related to platelet count at 1-month post-Kasai (OR 0.5, 0.19-0.99). Cluster analysis of infectious patterns identified three unique cohorts of patients based on their infection history: no/few infections (n = 18), mostly cholangitis (n = 20) or mixed infections (n = 27)., Conclusion: Variability of infection risk exists amongst children with BA. Age at Kasai and platelet count are risk factors for future infections, suggesting that patients with more severe disease are at greater risk. Cirrhosis associated immune deficiency may exist in chronic pediatric liver disease and should be the subject of future investigations in order to optimize outcomes., Competing Interests: Declaration of Competing Interest No other disclosures or conflicts of interest were reported., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.

Background: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis., Methods: Liver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed., Results: Immunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group., Conclusion: Activation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the accuracy of intraoperative hepatic subcapsular spider-like telangiectasia (HSST) sign for differentiating biliary atresia (BA) from other causes of hepatic cholestasis., Methods: The data of 69 patients with jaundice treated from January 2019 to December 2021 were retrospectively analyzed. Based on intraoperative cholangiography (IOC), the patients were divided into two groups: the BA group (n = 49) and the non-BA group (n = 20). The biochemistry tests, liver ultrasound, liver stiffness value and HSST sign of the two groups were compared., Results: The incidence of abnormal gallbladder, elevated γ-glutamyl transpeptidase (γ-GGT) > 182.0U/L and abnormal liver stiffness (> 6.4 kPa) in BA group were significantly higher than those in non-BA group (P < 0.001). The HSST sign was present in all BA patients and not found in non-BA group. The area under receiver operating curve of direct bilirubin(DBIL), γ-GGT, abnormal gallbladder, liver stiffness value and HSST sign were 0.53, 0.84, 0.78, 0.96, and 1.00, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of HSST sign in the diagnosis of BA were all 100%., Conclusion: Presence of HSST sign on diagnostic laparoscopy is highly suggestive of BA.It can be used in the differential diagnosis of BA and non-BA., Level of Evidence: Level III., (© 2023. The Author(s).)

Background: Biliary atresia (BA) is the most common cause of neonatal cholestatic syndrome. The true incidence of BA in Pakistan is largely unknown., Aim: This study aimed to report the clinical features, age at diagnosis and outcomes of biliary atresia from the first pediatric liver transplant center in Pakistan., Methods: The study was done in Shifa International hospital from 2013 to 2020. All babies who had biliary atresia confirmed by laboratory investigation were included. Demographic data, age of presentation, clinical presentation, supporting investigations like liver function tests, ultrasound abdomen, HIDA scan and liver biopsy were noted. Outcome related to Kasai portoenterostomy, liver transplant, complications and immunosuppressant agents were noted., Result: A total of 42 children were included, 23 (54.7%) males and 19 (45.2%) were females. Jaundice was seen in all patients (100%) followed by acholic stools (81%). Associated malformations were noted in 6 (14.2%) patients. Liver function tests confirmed obstructive cholestasis (p 0.04). Kasai was done in 19 (45%) patients only, living donor liver transplant was performed in 6 (14%) patients. Age range of transplant patients was from 3 months to 1 year. Indication for liver transplant was failed Kasai in 1(16.7%) patient and chronic liver disease in 5 (83.3%) patients. LDLT survivors were 10 months to 1 year of age at the time of transplant, mean age was 10.6 months. Maximum survival noted so far is 7 years. Acute complications seen post-transplant were sepsis (three patients), surgical site infections (two patients), biliary leaks and acute cellular rejection in one patient each. Chronic graft rejection, portal vein stricture needing stenting was done in one patient., Discussion: All patients underwent LDLT from related donors wih no donor related mortality. All are deceased patients were yonger and had advanced disease. BA remains third most commo indication of transplant in our center., Conclusion: Liver transplant is the only lifesaving procedure after failed Kasai or as primary liver transplant due to advance liver disease. The advent of liver transplantation services offers survival and improving outlook of the disease., (© 2022 Wiley Periodicals LLC.)