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Background Timely discriminating biliary atresia (BA) from other causes of cholestasis is important but challenging. Aims To develop a useful diagnostic nomogram and a simplified scoring system to diagnosing BA. Study design All medical records of the patients who were consecutively admitted to our institution with cholestasis from March 2016 to December 2020 were retrospectively searched. The patients were allocated to the derivation cohort (n = 343) and the validation cohort (n = 246). Multivariable logistic regression models were used to construct the nomogram. The nomogram was validated in both cohorts. The simplified risk score was derived from the nomogram. Results The nomogram was constructed based on presence of clay stool, gallbladder length, gallbladder emptying index, shear wave elastography value, and gamma-glutamyl transferase level. This model showed good calibration and discrimination ability, with the C-index of 0.968 (95% CI: 0.951–0.984). The discriminating ability is most prominent in the 61–90 days group, with AUC of 0.982 (95% CI: 0.955–1.000). The simplified risk score identified most patients with very high or low risk of BA, and was capable of exempting 64.3% non-BA patients from intraoperative cholangiogram procedure. Conclusions This novel diagnostic nomogram had good discrimination and calibration abilities. The simplified scoring system showed significant clinical utility.

Background/purpose Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Methods Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Results Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%). Conclusion Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Background Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). Methods Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P Results Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). Conclusions We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.

Introduction Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. Patients and methods The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. Results A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P Conclusions Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Introduction Liver transplantation is the only curative treatment for patients with end-stage liver disease. Neurological complications are one of the main causes of morbidity and mortality. Objective To study neurological complications after liver transplantation in paediatric patients. Methods We conducted a retrospective study, including all paediatric patients younger than 17 years undergoing liver transplantation over a 12-year period at our centre. Results Forty-six liver transplantations were performed in 38 patients. The most common indication was biliary atresia. Up to one-third of patients presented neurological complications, with psychomotor agitation being the most frequent. Incidence of neurological complications was significantly higher in the group of infants than in older age groups. Encephalopathy was more common in patients with acute liver failure than in those with chronic liver failure. Conclusions Neurological complications, and particularly psychomotor agitation, are common after liver transplantation in paediatric patients.

BACKGROUND Narrative nursing is an important clinical nursing intervention model. It is the practice of patient storytelling to share the essence of nursing. The current clinical intervention for biliary atresia (BA) mainly focuses on disease treatment and does not pay enough attention to the psychological state of family members. AIM To explore the application value of narrative nursing in the families of children with BA. METHODS Sixty-four family members of children with BA in our hospital from December 2017 to October 2020 were retrospectively included and were divided into a study group (n = 32) and a control group (n = 32). The control group was provided with routine nursing, while the study group was given narrative nursing on the basis of the control group. The scores of mood state (depression and anxiety), family members’ nursing ability, perceived stress, and nursing job satisfaction of the children’s families were calculated before and after the intervention. RESULTS Before intervention, there was no significant difference in the self-rating anxiety scale and self-rating depression scale scores between groups (P > 0.05). After intervention, the self-rating anxiety scale and self-rating depression scale scores in the study group were lower than those in the control group (both P = 0.000). Before intervention, the study group adjusted life to meet care needs, evaluated family members and social resources, dealt with personal emotions, responded to needs, and provided assistance, and the adaptive care role scores were not significantly different from those in the control group (P = 0.802, 0.819, 0.694, 0.796, and 0.686, respectively). After intervention, all scores were significantly lower in the study group than in the control group (all P < 0.0001). Before intervention, there was no significant difference in the child post-traumatic stress disorder symptom score (CPSS) score between groups (P = 0.615). After intervention, the CPSS scores were significantly lower than those before intervention in both groups and lower in the study group than in the control group (P < 0.0001). Nursing job satisfaction of the family members of the study group (93.75%) was higher than that of the control group (75.00%) (P = 0.039). CONCLUSION Narrative nursing with family members of children with BA can effectively alleviate negative emotions, reduce perceptual pressure, and improve nursing ability. Additionally, family members are more satisfied with nursing work.

Introduction Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include percutaneous transluminal angioplasty (PTA), with or without stent placement, mesorex bypass (MRB), splenorenal shunt, mesocaval shunt, endovascular recanalization (EVR), splenic artery embolization and splenectomy. However, specific characteristics of patients undergoing intervention and selection of individual treatment and its efficacy have remained unclear. This review systematically analyzed biochemical and clinical characteristics, selection of treatment, efficacy, and post-procedural complications. Methods We systematically searched PubMed and Embase between January 1995 and March 2021 for studies on the management of PVO after LT. We analyzed the reports for biochemical and clinical characteristics at the timing of the intervention in different patients, selection of treatment, and reported efficacies. Results We found 22 cohort studies with 362 patients who had the following characteristics: biliary atresia (83%), living-donor LT (85%), thrombocytopenia (73%), splenomegaly (40%), ascites (16%), or gastrointestinal bleeding (26%). The 3-year primary patency of PTA without stent placement was similar to that with stent placement (70%–80% and 43%–94%, respectively). MRB was used as an initial treatment with a 3-year patency of 75% to 100%. One study showed that 5-year primary patency of EVR was 80%. Secondary patency was 90% to 100% after 3 years in all studies with PTA alone, PTA/stent placement, and stent placement alone. Conclusion This is the first review of all treatment protocols in PVO after pediatric LT. We showed that an important group of patients has severe symptoms of portal hypertension. Efficacy of all treatment modalities was high in the included studies which make them important modalities for these patients.

Early diagnosis and timely surgical Kasai portoenterostomy greatly improve the survival of patients with biliary atresia (BA), a neonatal cholestatic disease, which has encouraged investigators to develop newborn screening for BA. In this study, we used ultraperformance liquid chromatography-triple quadrupole mass spectrometry-based targeted metabolomics profiling to identify potential BA biomarkers in dried blood spots (DBS) collected from BA patients (n = 21) and healthy controls (n = 100). A distinctive metabolic profile comprising eight significantly differentially expressed metabolites, taurohyocholic acid (THCA), glutamic acid, 2-hydroxyglutaric acid, ketoleucine, indoleacetic acid, alpha-ketoisovaleric acid, glycocholic acid, and taurocholic acid (TCA), clearly distinguished BA infants from control neonates. Three metabolites, THCA, 2-hydroxyglutaric acid, and indoleacetic acid, were selected using linear regression and receiver operating characteristic (ROC) curve analysis and model construction. The area under the ROC curve for this model to discriminate between BA and comparison infants was 0.938 (95% confidence interval, CI: 0.874-1.000). A cutoff value of -0.336 produced a sensitivity of 90.48% (95% CI: 69.62% - 98.83%) and specificity of 92% (95% CI: 84.84% - 96.48%). In conclusion, the results suggest that metabolic markers in DBS obtained from newborns have a great potential for BA screening.

"Biliary atresia (BA) is a common cause of jaundice in infancy. There is increasing evidence that newborn screening with direct or conjugated bilirubin leads to earlier diagnosis. Although the Kasai portoenterostomy is the primary treatment, there are scientific advances in adjuvant therapies. As pediatric patients transition to adult care, multidisciplinary care is essential, given the complexity of this patient population."

Purpose To evaluate the application value of two-dimensional shear wave elastography (2D-SWE) for non-invasive diagnosis of liver cirrhosis (LC) in patients with biliary atresia (BA) before Kasai portoenterostomy (KP), and the cutoff value of liver stiffness measurement (LSM) for diagnosing LC. Methods The clinical data of 51 patients with BA who were diagnosed via surgery and pathological results from May 2017 to December 2018 in the department of general surgery, Beijing Children's Hospital, Capital Medical University, were retrospectively analyzed. The liver tissue specimens obtained during KP were evaluated according to the METAVIR criteria. The LSM was obtained using the 2D-SWE technique before KP. Results There was a grade positive correlation between LSM and METAVIR staging, and the Spearman correlation coefficient was 0.432 (P = 0.002). The AUC for 2D-SWE diagnosing LC (METAVIR score S = 4) in patients with BA before KP was 0.843 (95% confidence interval 0.736 ~ 0.950). The best cutoff value was 16.05 kPa, and the corresponding sensitivity was 75.0%, specificity was 83.7%, positive predictive value (PPV) was 46.1%, negative predictive value (NPV) was 94.7%, and the accuracy was 82.4%. Conclusion 2D-SWE can be used to noninvasively diagnose LC in patients with BA before KP, and the cutoff value is 16.05 kPa.

Objectives: Biliary atresia (BA) is still an enigmatic disease. Deeper knowledge of its pathophysiology could help develop better treatments. SOX9 regulates bile duct development, liver regeneration and fibrosis; therefore, it could be determinant in characterizing BA liver damage. Aim: To study if there is a SOX9 expression pattern in liver biopsies from BA patients. Methods: Liver biopsies from BA patients (group BA), from age-matched infants without primary hepatic disease (group Control), and from patients with other liver conditions (group OLC) were compared. Expression of SOX9 was checked for: amount, intensity of immunoreaction, localization within ductular structures, perifibrotic epithelial cells, and lobular cells. The scores were added to create a scale from 0 to 11 that allowed group comparison. SOX9 Scale and liver survival were also looked for a correlation. Results: All BA cases had a score >4, while all controls scored

The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. The Wechsler Intelligence Scale for Children—fourth edition test was administered to 20 patients who survived $$\ge $$ 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

Background Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. Methods To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. Results BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. Conclusion These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.

Maralixibat (Livmarli™) is an orally-administered, small-molecule ileal bile acid transporter (IBAT) inhibitor being developed by Mirum Pharmaceuticals for the treatment of rare cholestatic liver diseases including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC) and biliary atresia. Maralixibat received its first approval on 29 September 2021, in the USA, for use in the treatment of cholestatic pruritus in patients with ALGS 1 year of age and older. Maralixibat is also under regulatory review for ALGS in Europe, and clinical development for cholestatic liver disorders including ALGS in patients under 1 year of age, PFIC and biliary atresia is continuing in several other countries. This article summarises the milestones in the development of maralixibat leading to this first approval for ALGS. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01649-0.

Introduction: Hospital Selayang started the liver transplant program in 2002. We report a total of 81 liver transplant cases until year 2015. Among these, paediatric cases constitute almost half. This report aims to review the demography and outcome of paediatric liver transplant cases. Methodology: Case notes of all paediatric patients underwent liver transplant from year 2002 to 2015 were retrospectively reviewed. Results: A total of 38 paediatric cases received liver transplantations from year 2002 to 2015. Age at transplantation ranged from 11 months to 16 years old (mean age 6 years) and weight ranged from 6.47 to 63 kilogram (mean 18kg). There were 20 males and 18 females, 20 of them were Malay, whereas Chinese and Indian were 13 and 4 respectively. Eighteen cases were living-related and 20 cases were cadaveric liver transplants. For recipient blood group, O+ is the commonest. Biliary atresia was the most common indication for liver transplant (22 cases; 58%), followed by intrahepatic cholestasis disorders (5 cases; 13%) and metabolic disease (4 cases; 10%). Post transplantation, there were 6 (16%) biliary complications, 12 (32%) vascular complications, 26 (68%) developed early onset infection, 13% had acute rejection and 2 graft failure. Out of the 38 transplants, 79% of them survive after 1 year, and 69.7% survive after 5 years. The common causes of mortality were sepsis and vascular complications. Conclusion: Despite limited resources, a successful paediatric liver transplant programme has been established in Hospital Selayang with good survival rate.

The objectives of this study is to compare the prognostic differences between cystic biliary atresia (CBA) and non-CBA, analyze the clinical and liver pathological differences between the two groups, and explore the possible factors that affect the native liver survival of infants with CBA after Kasai portoenterostomy (KPE). From 2013 to 2020, 131 infants with BA were admitted to Tianjin Children’s Hospital. A total of 108 infants with BA were included after excluding those who did not undergo surgery after diagnosis (n = 23), including 12 cases of CBA and 96 cases of non-CBA. The clinical data, native liver survival and liver pathology, including liver fibrosis, bile ductular proliferation (BDP), bile plug, and portal area inflammation infiltration of the two study groups were compared. CBA accounts for 9.16% (12/131) and type I CBA accounts for 6.87% (9/131) of all types of BA. 16.7% (2/12) of CBA were detected prenatally with diagnosis of choledochal cyst (CC). The age at KPE, total bilirubin, direct bilirubin, and total bile acid levels of CBA were significantly lower than those of non-CBA (P = 0.047, P = 0.013, P = 0.009, P = 0.010, respectively). The long and wide diameters of the gallbladder were significantly larger than those of non-CBA (both P

The aim is to explore the impact of the Kasai procedure (KP) and the length of native liver survival time (NLST) on outcomes of liver transplantation (LT). Patients with biliary atresia (BA), who underwent LT in Beijing Friendship Hospital from January 2017 to December 2019, were enrolled and divided into non-KP (N-KP) and post-KP (P-KP) groups. The patients in the P-KP group were further divided into early failure (KP-EF) defined by NLST 5years) subgroups. Clinical data at baseline and during follow-up were collected. The inverse probability of treatment weighting method was used to evaluate the independent effect of KP and the length of NLST on clinical outcomes. Among 197 patients with BA, the N-KP group accounted for 43 (21.8%), KP-EF 71 (46.1%), KP-MF 59 (38.3%), and KP-LF 24 (15.6%) cases, respectively. The N-KP and KP-EF groups had significantly longer hospitalization and intensive care unit stays after LT. Graft and overall survival rates were 93.0% in the N-KP group and 97.4% in P-KP group, respectively. The mortality rate in the P-KP group were significantly lower compared with that of the N-KP group with a hazard ratio (HR) of 0.2 (P=0.02). The risks of biliary and vascular complications and cytomegalovirus (CMV) infection after LT were significantly higher in KP-EF group than those in the KP-MF and KP-LF groups (HRs = 0.09, 0.2, and 0.3, respectively; all P&nbsp

Background Endoscopic variceal ligation (EVL) is a widely accepted treatment for esophagogastric varices in patients with portal hypertension. It is used for urgent treatment and prophylactic treatment of esophagogastric varices not only in adults, but also in pediatric patients. However, major life-threatening adverse events such as early rebleeding can occur. Although early rebleeding after EVL among children and adolescents has been reported, the risk factors remain obscure. This study evaluated the risk factors for early rebleeding after EVL in children and adolescents. Methods Subjects were children and adolescents with portal hypertension aged less than 18 years who underwent EVL for esophagogastric varices. Early rebleeding was defined as hematemesis, active bleeding or blood retention in the stomach, confirmed by esophagogastroduodenoscopy from 2 hours to 5 days after EVL. Results A total of 50 EVL sessions on 22 patients were eligible for this study. There were 4 episodes of early rebleeding. No other major adverse events have occurred. Multivariate analysis showed that EVL implemented at cardiac varices just below the esophagogastric junction (EGJ); within 5mm from the EGJ, is the independent factor of higher risk of early rebleeding: odds ratio 18.2 (95% Confidence interval: 1.40-237.0), p=0.02. Conclusions Children and adolescents who undergo EVL for cardiac varices just below the EGJ have a higher risk of early rebleeding than those who do not.

BACKGROUND AND AIMS: Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, i.e. the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE.METHODS: We compared feces of term born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ vs. without COJ (total serum bilirubin RESULTS: Alpha diversity was comparable between BA (n = 12, age 1.6[1.3-1.8]mo) and controls (n = 6, age 2.0[1.4-2.1]mo; P = 0.22). Compared to controls, BA patients had lower abundances of Bifidobacteriaceae (β=-1.98, P CONCLUSIONS: The gut microbiota of biliary atresia patients prior to Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive and mechanistic roles of the gut microbiota composition in bile homeostasis.

Perinatal liver inflammation can have life-threatening consequences, particularly in infants and young children. An example of a hepatic inflammatory disease during infancy is biliary atresia (BA), an obliterative cholangiopathy that rapidly progresses to hepatic fibrosis and liver failure. The aggressive nature of BA in neonates compared to the pathogenesis of inflammatory liver diseases in adults, suggests that the mechanisms responsible for restoring tissue homeostasis following inflammation are impaired in affected infants. This article reviews our recent findings demonstrating that the relative abundance of Ly6c

The article presents the current views on genetics, features of metabolic disorders, course of various clinical manifestations, diagnostic criteria, and treatment principles for monogenic enzymopathy — an inherited α1;antitrypsin (AAT) deficiency. Inherited AAT deficiency manifests itself as four clinical syndromes: respiratory disease (pulmonary emphysema, chronic obstructive pulmonary disease (COPD), bronchial asthma, spontaneous pneumothorax, bronchiectasis); liver disease and blood vessel damage. Respiratory disease manifests itself between the ages of 20–40 years. Chronic pulmonary emphysema is typical for homozygous PiZZ gene carriers. The most unfavorable clinical course variant including persistent cough, COPD development, bronchial asthma, pneumonia, co-existence of various respiratory diseases and severe disorders of external respiration is the PISZ phenotype. Bronchial asthma has severe clinical course with torpid purulent endobronchitis; is often uncontrolled despite background therapy. In COPD patients, exacerbations are frequent, severe, and prolonged. The reduction in the vessels of the pulmonary circulation results in pulmonary hypertension, right ventricular failure. In AAT deficiency, there is a high incidence of bronchiectasis, lung cancer. Liver diseases manifest themselves as neonatal hepatitis, biliary atresia, liver cirrhosis, infectious complications. Chronic form is characterized by subclinical changes in the biochemical parameters of liver function most of which (up to 70%) normalize before the age of 18 years. In patients until the age of 20 years, disease slowly progresses and leads to the development of liver cirrhosis in 30% of cases, while older patients develop liver cirrhosis in 30–50% of cases. Some patients have a benign course of liver disease and present with hepatomegaly. Hemorrhagic syndrome occurs when protease inhibitor gene product acquires the properties of antithrombin. Vascular disease manifests itself as necrotizing panniculitis, severe hemorrhagic vasculitis with serum antineutrophil cytoplasmic antibodies to proteinase (С-АNСА). AAT deficiency may coexist with systemic vasculitis, vascular aneurysm, many other diseases, as well as with the development of aplastic processes of various localization. In addition to clinical manifestations, diagnosis of inherited AAT deficiency includes screening programs, instrumental (X-ray, spirometry, ECG, ultrasound), laboratory (liver function, coagulation profile, immunogram, serum AAT concentration), genetic investigations, exclusion testing for cystic fibrosis, viral hepatitis, and other diseases. Treatment of patients with inherited AAT deficiency consists in adequate nutrition and physical activity; treatment of pre-existing conditions; prevention and timely therapy for respiratory infections; pathogenetic therapy. Pathogenetic therapy for AAT deficiency is a replacement (augmentation) therapy with exogenous α1-antitrypsin concentrate. Replacement therapy is indicated only in patients >18 years of age with the PiZZ phenotype or other rare AAT phenotypes. No conflict of interest was declared by the author. Key words: children, inherited α1-antitrypsin deficiency, diagnosis, therapy.

MicroRNAs (miRNAs) play an important role in regulating fibrogenesis in the liver. The current study examined the ability of microRNA-214 (miR-214) level in liver and serum samples obtained from patients with BA to predict progressive liver fibrosis in patients with biliary atresia (BA). We examined miR-214 level in relation to conventional markers of liver fibrosis, with liver and serum samples from BA patients. Fifty-two patients with BA who underwent Kasai portoenterostomy and four control patients underwent liver biopsy. In 28 patients with BA, blood samples were collected to analyze circulating serum miR-214. MiR-214 levels in liver tissue were significantly upregulated in patients with BA who had severe liver fibrosis (F3–4) compared to those with none to mild fibrosis (F0–2), whereas suppressors-of-fused homolog (Sufu) mRNA levels were significantly suppressed in F3–4. Serum miR-214 levels were significantly higher in patients with F3–4 compared with F0–2. Area under the curve analysis showed that the serum miR-214 cut-off level for predicting F3–4 was 0.805 (p = 0.0046). Hepatic overexpression of miR-214 is associated with progression of liver fibrosis in patients with BA, and the circulating miR-214 level may serve as a non-invasive predictor of liver fibrosis.

Kasai procedure (KP) and liver transplantation (LT) represent the only therapeutic options for patients with biliary atresia (BA), the most common indication for LT in the pediatric population. However, KP represents by no means a radical option but rather a bridging one, as nearly all patients will finally require a liver graft. More and more experts in the field of transplant surgery propose that maybe it is time for a paradigm change in BA treatment and abandon KP as transplantation seems inevitable. Inadequacy of organs yet makes this option currently not feasible, so it seems useful to find ways to maximize the efficacy of KP. In previous decades, multiple studies tried to identify these factors which opt for better results, but in general, outcomes of KP have not improved to the level that was anticipated. This review provides the framework of conditions which favor native liver survival after KP and the ones which optimize a positive LT outcome. Strategies of transition of care at the right time are also presented, as transplantation plays a key role in the surgical treatment of BA. Future studies and further organization in the transplant field will allow for greater organ availability and better outcomes to be achieved for BA patients.

Background. In young children, the most common liver disease leading to transplantation is biliary atresia. Liver transplantation has fundamentally improved the survival rate of children with biliary atresia. Studies on developmental outcomes in children are mostly limited to small samples; there are no such studies in the Russian Federation.Objective: to determine the cognitive outcomes in children undergoing one-stage or two-stage surgical treatment of biliary atresia.Materials and Methods. 83 children were divided into groups: 36 children underwent transplantation without previous surgical interventions (group 1), 47 children underwent the Kasai palliative portoenterostomy (group 2). Inclusion criteria: 24 months of age or younger at the moment of transplantation, no medical history of neurological pathology. All children were examined before transplantation and at 1, 3, 6 and 12 months after liver transplantation. Psychomotor development was assessed using the Griffiths Psychomotor Development Scale for children under 24 months (translated by E.S. Keshishian), the Griffiths Intellectual Development Scale for children aged 2 to 8 years, and the Modified Checklist for Autism in Toddlers, Revised, for children 16-30 months old.Results. All children had developmental delays at the time of transplantation. Up to 50% of the children had signs of cachexia, with a shoulder circumference of less than 3 percentile. Only two children showed obvious hepatic encephalopathy in the form of depressed consciousness. After liver transplantation, 94% of group 1 children recovered their preoperative psychomotor development levels, and only 68% in group 2 made these gains. At 3 and 6 months after transplantation, about 80% of group 1 children showed normal psychomotor development, whereas in group 2, only 61% did. By 12 months after liver transplantation, the difference between the groups was more evident: 83.3% of group 1 children and only 53.2% of group 2 children were developing according to age. The difference between the groups was statistically significant (p < 0.05).Conclusion. Children who received one-stage treatment of biliary atresia and underwent liver transplantation have better neuropsychological development within a year after surgery than children with two-stage surgical treatment.

It is difficult to distinguish cystic biliary atresia (CBA) from choledochal cyst (CC) before intraoperative cholangiography in neonates or young infants because of the similar ultrasonographic patterns and clinical manifestations. This study is to investigate the difference of clinical parameters between CBA and CC. 96 patients with cyst at hepatic hilum whose ages were less than 120 days during the period from Jan’2013 to Nov’2015 were retrospectively studied, they were divided into CBA group and CC group by intraoperative cholangiography, there were 29 cases of CBA and 67 cases of CC. It was compared and analyzed on laboratory data, preoperative ultrasonographic features, intraoperative cholangiography and histopathological results between the two groups. Data were quoted as means ± standard deviation (SD) or median (range), Student’s t test, non-parametric test and χ2 test were used as appropriate. P

In biliary atresia (BA), the ultrasonic triangular cord (TC) sign is positive at ≥ 3 mm, but sometimes there is BA even if it is ≤ 3 mm. For improving the ultrasonographic diagnosis, we have established a new evaluation, adding the ratio of the anterior/posterior thickness (TC ratio) in the hyperechoic area and the presence of a cystic lesion in the triangular cord (TCC). We examined 24 cases of suspected BA who demonstrated acholic stools from 2006 to 2020. We retrospectively reviewed the timing of ultrasonographic diagnosis, the gallbladder diameter, gallbladder mucosal irregularity, the TC sign, TCC, and the TC ratio. In the BA group (n = 10) vs the Non-BA group (n = 14), the age at ultrasonography was 75 ± 41.7 vs. 81 ± 39.1 days (p = 0.72), the gallbladder diameter was 12.1 ± 9.7 vs. 24.2 ± 6.96 mm (p = 0.02), irregularity of gallbladder mucosa was 7 cases vs. 1 case (p

Four male infants with cystic fibrosis and prolonged neonatal jaundice underwent Kasai procedure to relieve biliary obstruction due to apparent biliary atresia. The excised remnants had viscid mucus accumulation in hypoplastic gallbladders and distended peribiliary glands. Main hepatic ducts were narrow and/or malformed. Microscopic differences between the gallbladder and extrahepatic bile ducts in cystic fibrosis and sporadic biliary atresia were unequivocal, despite some histologic overlap; no erosive or fibro-obliterative lesions typical of biliary atresia were seen. Common in liver, biopsies were small duct cholangiopathy with intense focal cholangiolitis and massive accumulation of ceroid pigment within damaged cholangiocytes, and in portal macrophages, portal fibrosis, and unequivocal features of large duct obstruction were inconspicuous compared with biliary atresia. Plugs of bile in small ducts tended to be pale and strongly periodic acid-Schiff-reactive in cystic fibrosis. Distinguishing the liver lesion from that of biliary atresia is challenging but possible. Liver biopsies from 2 additional infants with cystic fibrosis and prolonged jaundice that spontaneously resolved showed a similar small duct cholangiopathy. Small gallbladders and extrahepatic ducts challenge surgical judgment as findings in liver biopsies challenge the pathologist. The decision to perform a Kasai procedure is reasonable when mimicry of biliary atresia is grossly complete. We hypothesize that a disorder of bile volume/flow during development and/or early infancy linked to the CFTR mutation alone or in combination with the stresses of neonatal intensive care causes destructive cholangiolitis and intrahepatic reduction of bile flow with secondary hypoplasia of extrahepatic biliary structures.

The matrix metalloproteinase-7 (MMP-7) is a promising marker for identification of biliary atresia. We assessed the accuracy and clinical value of MMP-7 for diagnosis of biliary atresia in infants. We searched MEDLINE, Embase, ISI Web of Knowledge, and the Cochrane Library, from inception to December 30, 2020. We included articles written in English, Chinese, or French that investigated MMP-7 for differentiation of biliary atresia infants from those with other form of cholestasis. Two review authors independently assessed eligibility for inclusion, evaluated the methodological quality of included studies, and extracted data to estimate diagnostic accuracy. We calculated individual and pooled sensitivities and specificities. We used I2 to test heterogeneity and investigated the source of heterogeneity. Our search identified 4 studies (593 infants). Risk of bias in the included studies was generally low. Bivariate analysis yielded a mean sensitivity of 0.96 (95% CI: 0.93–0.98) and specificity of 0.91 (95% CI: 0.85–0.95). The area under the receiver operating characteristic curve was 0.97 (95% CI: 0.95–0.98). A moderate heterogeneity was found among the included studies as the I2 values for sensitivity and specificity were 8.6% (95% CI: 1.5–19.04) and 56.7% (95% CI: 28.91–70.07), respectively. After a sensitivity analysis, there was no change in sensitivity and MMP-7 specificity ranged from 0.91 to 0.93. The serum MMP-7 is a helpful biomarker for diagnosis of biliary atresia in cholestasis infants. Nevertheless, it cannot be recommended as the single definitive test for biliary atresia diagnosis; further primary clinical research is mandatory. Trial registration: prospero230839

A disfunção precoce de enxerto hepático consiste em uma síndrome multifatorial caracterizada por alterações clínicas e laboratoriais associadas à alta morbidade nos primeiros dias pós-transplante. Relacionada à lesão de isquemia e reperfusão do fígado, pode levar em sua forma mais grave a alterações sistêmicas abruptas. Apesar de ser um quadro grave, as alterações podem ser transitórias, possibilitando recuperação do enxerto hepático. Sua ocorrência em população pediátrica é rara. A N-acetilcisteína, comumente utilizada no tratamento de hepatotoxicidade secundária à overdose por paracetamol, tem surgido como alternativa eficaz na melhora clínica de pacientes transplantados com má função de enxerto. Relatamos um caso de paciente do sexo masculino, dois anos, submetido a transplante de fígado por atresia de vias biliares, sem intercorrências intraoperatórias. Evoluiu com quadro de disfunção precoce grave de enxerto no segundo dia pós-operat óio, sem boa resposta às medidas de suporte, cogitando-se indicação de retransplante. Foi iniciada administração de n-acetilcisteína, dosagem de 100mg três vezes ao dia, progredindo com melhora clínica significativa, sobretudo da função hepática. O acompanhamento de dados clínicos e laboratoriais de pacientes no período pós-transplante é fundamental, tendo em vista riscos e graves repercussões da disfunção precoce do enxerto hepático. A N-acetilcisteína é uma droga que tem sido relatada atuando no aumento da oferta de oxigênio tecidual e na remodelação dos hepatócitos, a partir da recuperação dos níveis de glutationa. Os efeitos em pacientes com disfunções hepáticas pós -transplante têm sido promissores nos poucos relatos científicos de seu uso, como o caso em questão.

Background Congenital biliary atresia is a type of obstruction of the bile ducts inside and outside the liver, which can lead to cholestatic liver cirrhosis and eventually liver failure. The preduodenal portal vein (PD-PV) is a rare developmental malformation of the PV. The PV courses in front of the duodenum. However, very few cases of neonatal biliary atresia combined with PD-PV have been reported in the scientific literature. Case summary A 1-mo-and-4-d-old child was admitted to the hospital in January because of yellowish skin. After surgical consultation, surgical intervention was recommended. The child underwent Hilar-jejunal anastomosis, duodenal rhomboid anastomosis, and abdominal drainage under general anesthesia. During the operation, the PV was located at the anterior edge of the duodenum. Conclusion Diagnoses: (1) Congenital biliary atresia; (2) PD-PV; and (3) Congenital cardiovascular malformations. Outcomes: Recommendation for liver transplantation. Lessons: The choice of treatment options for neonatal biliary atresia combined with PD-PV.

Back ground. Liver transplantation is an effective treatment for acute or chronic liver failure and metabolic liver disease, which is associated with good quality of life in over 80 percent of recipients. We aimed to evaluate outcome of duct-to-duct vs. Roux-en-Y hepaticojejunostomy biliary anastomoses in pediatric liver transplant recipients below 15-kg.Methods. In this single-center retrospective study, all children less than 15 kg that have undergone liver transplantation at Nemazee Hospital Organ Transplant Center affiliated with Shiraz University of Medical Sciences from 2009 till 2019, were enrolled. Over a 10-yr period, 181 liver transplants were performed in patients with two techniques including duct-to-duct (Group 1) vs. Roux-en-Y hepaticojejunostomy biliary anastomoses (Group 2). All data was collected from patients’ medical records, operative notes, and post-transplant follow up notes. Data was analyzed by SPSS software V21.Results. Overall, 94 patients had duct to duct anastomosis (group 1) and 87 cases had Roux-en-Y hepaticojejunostomy (group 2). The mean age of the patients was 2.46 ± 1.5. The most common underlying diseases was biliary atresia (32%). The most prevalent complication after the surgery was infection in both groups. cardiopulmonary problems were significantly higher in group 2 (24.1% vs 4.3%) (p < 0.001). The rate of infection was significantly higher in group 2, as well.Conclusion. Our study showed a relatively high rate of post-operative infection which was the most among patients who had undergone Roux-en-Y hepaticojejunostomy. Except from biliary complications which were mostly observed in DD group, other complications were more common among Roux-en-Y group.

The effectiveness of laparoscopic Kasai portoenterostomy (Laparoscopic-KPE) for biliary atresia (BA) has been reported but remains controversial. We reviewed our own cases and cases described in previous studies of liver transplantation (LT) for BA after Laparoscopic-KPE to investigate the efficacy of Laparoscopic-KPE. Subjects were children of ≤ 2 years old with LT for BA after KPE who underwent Laparoscopic-KPE (n = 10) or Open-KPE (n = 115) between 2009 and 2020. Propensity score matching was performed to reduce the effect of treatment selection bias. The clinical data regarding the preoperative characteristics and surgical results were compared. The rates of hypoplastic portal vein and retrograde portal vein flow were lower in the Laparoscopic-KPE group than in the Open-KPE group (0 vs. 40.0%, p = 0.02 and 0 vs. 35.0%, p = 0.04). There was no marked difference in the operation time or duration of hepatectomy. For portal vein reconstruction, a vein graft was not required in the Laparoscopic-KPE group (0 vs. 35.0%, p = 0.03). No patients in the Laparoscopic-KPE group developed portal vein complications or required re-laparotomy for bowel perforation or re-bleeding, in contrast to the Open-KPE group (0 vs. 15.0% and 0 vs. 10.0%, respectively). Laparoscopic-KPE may reduce postoperative complications that necessitate re-laparotomy in LT.

To assess the utilization of SCC implemented in southern India and the effect on SCC utilization of face-to-face verbal education versus video-based content delivery. The study included newborns with postnatal age of less than 2 wk at discharge. Mothers were administered SCCs and provided standardized verbal or video health education based on the time-period of enrollment. Home based monitoring of stool color and return of SCC on postnatal day 21 was advised. Telephone surveys were conducted to identify SCC use among families that did not return the SCC by post. Of the 2254 newborns enrolled, 1130 were in the verbal-counseling group and 1124 in the video-counseling group. No newborns with pale stools and biliary atresia were identified. SCC return rates were 3.8% and 2.8%. Comparing the verbal and video-counseling groups, there were no differences in the conservative (81.8% vs. 81.5%) and optimistic estimates (97.1% vs. 97.3%) of SCC utilization rates. Mothers with better educational status had higher optimistic estimates of SCC utilization. The use of a validated SCC in Tamil with standardized information delivery leads to good utilization rates in southern India, with video content delivery being as effective as face-to-face verbal content delivery. SCC return by post is not a feasible mode of identification of card use. The study is registered under Clinical Trials Registry - India (CTRI/2018/01/011285).

PURPOSE OF THE REVIEW: Biliary atresia (BA) is the leading cause of chronic liver disease and the most common indication for pediatric liver transplantation. The use of ultrasound (US) and related techniques continues to evolve help diagnose BA as well as potentially to help predict outcomes after treatment with the Kasai portoenterostomy (KP). RECENT FINDINGS: There are no US findings which are definitive for BA; however, signs which are consistent with BA include gallbladder abnormalities, the triangular cord sign, presence of hepatic subcapsular flow, and hilar lymphadenopathy. Elastography techniques to measure liver stiffness may also increase the diagnostic accuracy of detecting BA, particularly in older infants or without other ultrasound findings. In addition, both US and elastography are still being studied as potential methods to predict outcomes after KP such as development of portal hypertension and need of for liver transplant. SUMMARY: US findings in the diagnosis of BA are well-characterized. Future studies will help determine the utility of elastography in diagnosing BA, as well as both US and elastography in monitoring and predicting disease outcomes after KP.

We present a case of pediatric deceased donor liver transplantation using a reduced whole liver graft in a 25-month-old boy weighing 12.7 kg. After he had undergone Kasai portoenterostomy for biliary atresia, his general condition deteriorated progressively. He was enrolled on the waiting list for liver transplantation with Pediatric End-stage Liver Disease score of 15. The donor was a 51-monthold boy with body weight of 20 kg. The donor-to-recipient body weight ratio was 158%. The liver graft appeared to be larger than the recipient's abdominal cavity. Thus, we planned to do in situ size reduction. Recipient surgery was performed following standard procedures. We performed graft outflow vein reconstruction using a modified piggyback technique like the double inferior vena cava method. Since the portal vein was hypoplastic, a side-to-side anastomosis technique was used. We also performed intraoperative portogram to embolize venous collaterals. After completing the graft implantation, we found that the liver graft was too large to be accommodated within the abdomen. After in situ resection of the left lateral section parenchyma, we successfully performed primary closure of the abdominal wound. This patient experienced episodes of acute rejection. He has been doing well for four years after the transplantation.

Background and Aims: Biliary atresia (BA) is a devastating cholangiopathy of infancy. Upon diagnosis, surgical reconstruction by Kasai hepatoportoenterostomy (HPE) restores biliary drainage in a subset of patients, but most patients develop fibrosis and progress to end-stage liver disease requiring liver transplantation for survival. In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling that of human BA. High-mobility group box 1 (HMGB1) is an important member of the danger-associated molecular patterns capable of mediating inflammation during infection-associated responses. In this study, we investigated the role of HMGB1 in BA pathogenesis. Approach and Results: In cholangiocytes, RRV induced the expression and release of HMGB1 through the p38 mitogen-activated protein kinase signaling pathway, and inhibition of p38 blocked HMGB1 release. Treatment of cholangiocytes with ethyl pyruvate suppressed the release of HMGB1. Administration of glycyrrhizin in vivo decreased symptoms and increased survival in the murine model of BA. HMGB1 levels were measured in serum obtained from infants with BA enrolled in the PROBE and START studies conducted by the Childhood Liver Disease Research Network. High HMGB1 levels were found in a subset of patients at the time of HPE. These patients had higher bilirubin levels 3 months post-HPE and a lower survival of their native liver at 2 years. Conclusions: These results suggest that HMGB1 plays a role in virus induced BA pathogenesis and could be a target for therapeutic interventions in a subset of patients with BA and high HMGB1.

This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Biliary atresia is challenging to diagnose because many of the clinical and imaging features of this condition overlap with those of other causes of cholestasis in newborns. When jaundice persists beyond 2 weeks of age, the neonate should be evaluated for cholestasis, and biliary atresia - the most common cause of neonatal cholestasis - should be considered. It is critical to diagnose biliary atresia early because failure to treat can result in hepatic fibrosis and death in less than 1 year. In this paper, we review the current diagnostic imaging methods, differential considerations and treatment options for biliary atresia.

Hepatoportoenterostomy remains the cornerstone of treatment for biliary atresia. Current employed techniques include laparoscopy and open surgery. This study aims to determine if either method provides an advantage. Following PRISMA guidelines, a systematic review was conducted. Nineteen studies were included. Mean operative time 34.98 (95% CI 20.10, 49.85; p ≤ 0.00001) was longer in laparoscopic while bleeding volumes - 16.63 (95% CI - 23.39, - 9.86; p ≤ 0.00001) as well as the time to normal diet - 2.42 (95% CI - 4.51, - 0.32; p = 0.02) were lower in the laparoscopic group. No differences were observed in mean length of stay - 0.83. Similar complication, transfusions, postoperative cholangitis 0.97, and transplant free survival rates 1.00 (0.63, 1.60; p = 0.99) were seen between groups. Laparoscopic portoenterostomy provides advantages on operative time and bleeding as well as to normal diet when compared to open procedures. Both procedures showed no differences in length of stay, complications, cholangitis, and importantly, native liver survival. Level of evidence: III.

Liver transplantation (LT) for small infants6 months old is rare but becoming common as perioperative care improves. In Taiwan, living donor LT (LDLT) has expanded indications but is rarely performed for this age group because of unfavorable outcomes in the literature. We evaluated LDLT outcomes of patients6 months old.We identified infants6 months old undergoing LDLT between 2004 and 2019 at our hospital. Variables related to recipients, donors, surgeries, and outcomes were analyzed.Nine patients were identified. Indications for LT were biliary atresia (n = 2), Alagille syndrome (n = 1), protein C deficiency (n = 1), and acute liver failure (n = 5), including two patients with neonatal hemochromatosis, one with herpes simplex hepatitis, one with giant cell hepatitis with autoimmune hemolytic anemia, and one with hemophagocytic lymphohistiocytosis. Median age and weight at LT were 129 days and 4.8 kg, respectively. Graft types included left lateral segment (LLS, n = 4), hyper-reduced LLS (n = 4), and monosegment (n = 1). The median graft-to-recipient weight ratio was 4%. The median follow-up period was 14 months (range, 8 days to 127 months) with two mortalities, and two patients were totally weaned off immunosuppressants. Adjuvant therapies were required for patients with giant cell hepatitis and hemophagocytosis. Preoperative reconstructive imaging for estimating graft thickness facilitated surgical planning.Although LDLT is difficult to perform for small infants, outcomes are favorable and mainly dependent on underlying causes in addition to technical innovations.

The spectrum of pathologies affecting the biliary tree in the pediatric population varies depending on the age of presentation. While in utero insults can result in an array of anatomic variants and congenital anomalies in newborns, diverse acquired biliary pathologies are observed in older children. These acquired pathologies display different presentations and consequences than adults. Multimodality imaging assessment of the pediatric biliary system is requisite to establishing an appropriate management plan. Awareness of the imaging features of the various biliary pathologies and conveying clinically actionable information is essential to facilitate appropriate patient management. In this paper, we will illustrate the anatomy and embryology of the pediatric biliary system. Then, we will provide an overview of the imaging modalities used to assess the biliary system. Finally, we will review the unique features of the pediatric biliary pathologies, complemented by histopathologic correlation and discussions of clinical management.

Biliary atresia (BA) is a progressive destructive cholangiopathy of unknown etiology that presents in early infancy. It has a worldwide frequency of 1:8,000–1:15,000 and is common in Asia than in the west. Based on the level at which the lumen of the extrahepatic duct is obliterated, BA is classified into three types. Type III is the commonest (∼85%) type and has the most proximal level of obstruction in the porta hepatis, while type II in which the atresia is at the level of the common hepatic duct, is the least common (∼2.5%) and has been rarely reported. Here, we report the imaging features of an infant with type IIB biliary atresia.

BACKGROUND/PURPOSE The biliary atresia (BA) inflammatory process leads to various obstructive patterns of extrahepatic biliary trees. The significance of the various BA obstructive patterns is unclear. This study aimed to determine the relationship between the anatomical patterns of the biliary tract and short- and long-term prognoses in BA. METHODS Between 1989 and 2018, 3483 patients were registered in the Japanese Biliary Atresia Registry. For this study, we selected 2649 patients who underwent Kasai portoenterostomy (KP) between the ages of 31 and 90 days to eliminate the influence of age at KP as much as possible. RESULTS Regarding the main type, there were significant differences in the jaundice clearance rate (JCR; Type I: 67.9%, Type I-cyst: 79.4%, Type II: 74.5%, Type III: 60.9%; P

Choledochal cyst (CC) is a cystic disease predominantly involving the extrahepatic biliary tree. Biliary atresia (BA), another disorder of the extrahepatic biliary tree, is sometimes considered to be in the same spectrum as pediatric CC. Recently, the absence and/or the structural abnormality of the primary cilia in the intrahepatic cholangiocytes have been implicated in the pathogenesis of BA. We aimed to evaluate the expression of primary ciliary proteins in the intrahepatic cholangiocytes in cases of pediatric CC and compare it with normal control and BA. We performed immunohistochemistry for primary ciliary proteins (acetylated-α-tubulin and double-cortin domain containing 2) on the liver biopsies of control liver (n=5), pediatric CC (n=13), and BA (n=14). We also compared the expression with various clinical, biochemical, histopathologic (portal fibroinflammation and ductal plate malformation), and immunohistochemical (proliferative index) data. There was significant loss of primary cilia from the intrahepatic cholangiocytes in cases of CC and BA as compared with the normal control by both immunostains (CC: P=0.003 and 0.001, respectively; BA: P=0.001 and 0.001, respectively). There was no significant difference between the CC and BA in terms of ciliary protein loss. The loss of the ciliary proteins occurred irrespective of the proliferative (MIB-1 labeling) index, portal fibroinflammation, or ductal plate malformation. The loss of cilia did not correlate with the clinical follow-up in cases of pediatric CC. The loss of primary cilia from the intrahepatic cholangiocytes may be crucial in the etiopathogenesis of pediatric CC.

Immunoproliferative small intestinal disease is an extranodal marginal zone B-cell lymphoma that arises from mucosa-associated lymphoid tissue and is associated with defective α heavy chain protein secretion. We present a case of an 18-year-old male patient admitted with diarrhea and weight loss who had previously received a liver transplant at the age of 19 months to treat biliary atresia. He underwent a thorough investigation and was diagnosed with immunoproliferative small intestinal disease lymphoma. The patient was switched from tacrolimus to everolimus and commenced on doxycycline treatment for 6 months and achieved long-term remission. Currently, 7 years after diagnosis, he is asymptomatic without evidence of histological relapse. This is the first case of immunoproliferative small intestinal disease described in a liver transplant recipient.

Summary Neonatal cholestatic liver disease is rarely encountered by pathologists outside of specialized pediatric centers and navigating the long list of potential diseases can be daunting. However, the differential diagnosis can be rapidly narrowed through open conversations between the pathologist and pediatric gastroenterologist. The dialog should ideally begin before obtaining the liver biopsy and continue through the rendering of the final pathologic diagnosis. Such dialogs are necessary to first ensure the proper handling of the precious sample and then to allow for synthesis of the clinical, laboratory, imaging, and genetic data in the context of the histologic features seen in the liver biopsy. In this review, we aim to provide a broad template on which such dialogs may be based and pitfalls that may be encountered on both the clinical and pathologic sides. This review will focus on non-biliary atresia etiologies of neonatal cholestasis, including select infectious, genetic, and metabolic entities.

Successful portoenterostomy (SPE) improves the short-term outcome of patients with biliary atresia (BA) by relieving cholestasis and extending survival with native liver. Despite SPE, hepatic fibrosis progresses in most patients, leading to cirrhosis and a deterioration of liver function. The goal of this study was to characterize the effects of SPE on the BA liver transcriptome. We used messenger RNA sequencing to analyze global gene-expression patterns in liver biopsies obtained at the time of portoenterostomy (n = 13) and 1 year after SPE (n = 8). Biopsies from pediatric (n = 2) and adult (n = 2) organ donors and other neonatal cholestatic conditions (n = 5) served as controls. SPE was accompanied by attenuation of inflammation and concomitant up-regulation of key extracellular matrix (ECM) genes. Highly overexpressed genes promoting biliary fibrosis and bile duct integrity, such as integrin subunit beta 6 and previously unreported laminin subunit alpha 3, emerged as candidates to control liver fibrosis after SPE. At a cellular level, the relative abundance of activated hepatic stellate cells and liver macrophages decreased following SPE, whereas portal fibroblasts (PFs) and cholangiocytes persisted. Conclusion: The attenuation of inflammation following SPE coincides with emergence of an ECM molecular fingerprint, a set of profibrotic molecules mechanistically connected to biliary fibrosis. The persistence of activated PFs and cholangiocytes after SPE suggests a central role for these cell types in the progression of biliary fibrosis.

Biliary atresia is managed surgically by the Kasai portoenterostomy (KP). It has been reported by some groups that the outcomes of patients who have an early failed KP requiring a liver transplant (LTx) within the first year of life are worse than the outcomes of patients who undergo a primary LTx. The aim of this study was to identify preoperative parameters that could help predict what patients are at risk for the early failure of the procedure. We conducted a retrospective chart review of all patients who underwent a KP between January 2008 and May 2018. The following preoperative parameters were analyzed: age at KP, anatomical variant of the biliary atresia, degree of liver fibrosis, CMV status, and PELD score. The main outcome of the study was the early failure of the KP (EF-K), which was defined as the need for LTx before 1 year of age, or BA-related death before 1 year of age. Second, we analyzed the risk factors associated with death without LTx within the first year of life. A total of 58 patients were included in the analysis. The native liver survival (NLS) was 56.5% and 48% at 1 and 5 years post KP, respectively. Overall survival (OS) was 79% and 76% at 1 and 5 years post KP, respectively. Early failure of KP occurred in 23 (39.7%) patients. OS in this group was 47% and 40% at 1 and 5 years, respectively. On the contrary, the OS of the remaining 35 (60.3%) patients was 100% at 1 and 5 years (P 4, and the PELD score. Nevertheless, on multivariate analysis, only PELD score was found as a statistically significant variable. Due to bad prognosis found in EF-K patients, we believe that it could be reasonable to offer them a primary LTx. PELD score was found to be the strongest preoperative parameter that allows predicting which patient will likely have an early failed KP. Further prospective and multicenter studies are needed to reinforce these results.