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Aim Methods Results Conclusions Inchinkoto (ICKT) is administered to patients with biliary atresia (BA) after surgery. Gardeniae fructus which is contained in ICKT is reported to be associated with idiopathic mesenteric phlebosclerosis (IMP). We investigated the influence of ICKT on calcification of the mesenteric veins suspected of IMP in BA patients.All BA patients with native liver survival who received ICKT after Kasai portoenterostomy were reviewed. All patients underwent abdominal computed tomography (CT) during treatment. Calcification of the mesenteric veins on the most recent CT scan after the initiation of ICKT was assessed.Twenty patients (6 males and 14 females) were enrolled in this study. Of these patients, 17 (85.0%) and 10 (50%) patients had used ICKT for ≥5 years and >10 years, respectively. Calcification of the mesenteric veins was detected in one patient, who was a 14 year old girl. The total dosage of Gardeniae fructus was 21 800 g.The incidence of calcification of the mesenteric veins in BA patients receiving ICKT was low. However, it is necessary to be aware that ICKT containing Gardeniae fructus is associated with the risk of developing calcification of the mesenteric veins suspected of IMP. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to compare the outcomes of pediatric LT with left liver grafts, obtained either from a living donor (LD) or a split deceased donor (sDD). Methods: Retrospective single‐center study from 2002 to 2022. All pediatric LT with left liver grafts (not including middle hepatic vein) from LD or sDD were included. Reduced grafts were not included. Results: A total of 112 pediatric LT were performed: 58 with LD grafts and 54 with sDD grafts (17 split ex situ and 37 in situ). Donor characteristics were similar, apart from donor age (33 years in LD vs. 30 years in sDD, p = 0.03). Indications were similar with 55% biliary atresia in each group. Retransplantation was more frequently performed in the sDD group (2% vs. 15%, p = 0.01). Recipient age, weight, and PELD score at transplant were not significantly different between groups. Cold ischemia time was longer for sDD (158 min in LD vs. 390 min in sDD; p < 0.0001). Posttransplant peak ALT was higher with sDD grafts (1470 vs. 1063, p = 0.018), and hospital stay was longer with sDD grafts (27 vs. 21 days, p = 0.005). However, there was no difference between groups in terms of major morbidity (Dindo‐Clavien grade ≥3), vascular and biliary complications, and 90‐day mortality. Patient survival at 10 years was 93.1% for LD and 92.8% for sDD (p = 0.807). Graft survival at 10 years was 89.7% for LD and 83.1% for sDD (p = 0.813). Conclusions: Technically similar LD and sDD grafts achieve very similar postoperative and long‐term outcomes with excellent patient and graft survival. [ABSTRACT FROM AUTHOR]

Background: Kinesin family member 12 (KIF12) mutation‐related cholestatic disorder represents a rare subtype of progressive familial intrahepatic cholestasis (PFIC), referred to as PFIC Type 8, with only 21 reported cases globally to date. Methods: Here, we present a unique case of a 6‐month‐old boy diagnosed with homozygous KIF12 gene mutation, who successfully underwent a living donor liver transplant at our center for end‐stage liver disease. Results: This case marks the youngest patient of KIF12‐related cholestatic disorder necessitating a liver transplant to date. The child initially presented with neonatal cholestasis and then developed infantile hepatic decompensation. Our report discusses the diagnostic process and management strategies employed. It underscores the importance of prompt diagnosis through clinical suspicion, biochemical parameters, and genetic testing, as well as the adoption of suitable management strategies, including the early contemplation of liver transplant in such exceptional and rare cases of genetic intrahepatic cholestasis. Conclusion: KIF12‐related genetic disease should be considered in neonatal cholestasis cases with high gamma glutamyl transpeptidase to differentiate from conditions like biliary atresia. Favorable outcomes post liver transplant stress the importance of early genetic testing and referral to liver transplant centers for unresponsive patients, potentially saving lives. [ABSTRACT FROM AUTHOR]

To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA− cohort, 70 (65.4%) in the DNA+ and AVT− cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log‐rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5‐year NLS of 68.3% in the DNA− cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT− cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5‐year NLS and AVT was recommended for CMV‐infected BA infants. [ABSTRACT FROM AUTHOR]

Aim: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. Methods: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. Results: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. Conclusion: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment. [ABSTRACT FROM AUTHOR]

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two‐dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B‐related cirrhosis (Hep‐B‐cirrhosis, n = 35). Then, three‐dimensional (3D) OPV was measured by X‐ray phase‐contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post‐necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep‐B‐cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre‐sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Sir Roy Calne in 1976 described "Biliary reconstruction is the Achilles heel of liver transplantation," and it remains true. In some patients, such as those with short‐gut syndrome and concomitant biliary atresia, neither duct to duct nor Roux biliary reconstruction is feasible. Methods: We present a case of child's third liver transplant (LT), where an innovative extra‐anatomical biliary bypass was created using a sleeve from greater curvature of the stomach. Results: The patient is well nearly 10 years following the LT. Conclusions: This technique could prove to be an important addition to the armamentarium of a surgeon in difficult retransplants and in patients with short‐gut syndrome as it provides a viable option with good long‐term outcome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin‐3, a beta‐galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin‐3 levels in children with BA. Methods: Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin‐3 was measured using standard enzyme‐linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. Results: Plasma Galectin‐3 in late BA was significantly higher than in early BA (20.82 [12.45–30.46] vs. 11.30 [8.74–16.83] ng/mL, p = 0.0096). Galectin‐3 levels correlated with markers of disease severity and interleukin‐6. There were significantly more Galectin‐3+ M2 macrophages in late BA in comparison to late other CLD (162 [157–233] vs. 49 [33–59] cells/mm2, p = 0.03). The number of Galectin‐3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. Conclusions: Plasma Galectin‐3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin‐3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin‐3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA. [ABSTRACT FROM AUTHOR]

Aims: Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. Methods: In this prospective cross‐sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two‐dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow‐up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. Results: Twenty‐five patients (aged 0–18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut‐off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase‐to‐platelet ratio index (APRI) instead of the platelet count with cut‐off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. Conclusions: A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Improved outcomes of liver disease in childhood and young adulthood have resulted in an increasing number of young adults (YA) entering adult liver services. The adult hepatologist therefore requires a working knowledge in diseases that arise almost exclusively in children and their complications in adulthood. Aims: To provide adult hepatologists with succinct guidelines on aspects of transitional care in YA relevant to key disease aetiologies encountered in clinical practice. Methods: A systematic literature search was undertaken using the Pubmed, Medline, Web of Knowledge and Cochrane database from 1980 to 2023. MeSH search terms relating to liver diseases ('cholestatic liver diseases', 'biliary atresia', 'metabolic', 'paediatric liver diseases', 'autoimmune liver diseases'), transition to adult care ('transition services', 'young adult services') and adolescent care were used. The quality of evidence and the grading of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: These guidelines deal with the transition of YA and address key aetiologies for the adult hepatologist under the following headings: (1) Models and provision of care; (2) screening and management of mental health disorders; (3) aetiologies; (4) timing and role of liver transplantation; and (5) sexual health and fertility. Conclusions: These are the first nationally developed guidelines on the transition and management of childhood liver diseases in adulthood. They provide a framework upon which to base clinical care, which we envisage will lead to improved outcomes for YA with chronic liver disease. [ABSTRACT FROM AUTHOR]

Background: Portal vein thrombosis is a potentially devastating complication following pediatric liver transplantation. In rare instances of complete portomesenteric thrombosis, cavoportal hemitransposition may provide graft inflow. Here we describe long‐term results following a case of pediatric cavoportal hemitransposition during liver transplantation and review the current pediatric literature. Methods: A 9‐month‐old female with a history of biliary atresia and failed Kasai portoenterostomy underwent living donor liver transplantation, which was complicated by portomesenteric venous thrombosis. The patient underwent retransplantation with cavoportal hemitransposition on postoperative day 12. Outcome: The patient recovered without further complication, and 10 years later, she continues to do well, with normal graft function and no clinical sequelae of portal hypertension. CT scan with 3‐D vascular reconstruction demonstrated recanalization of the splanchnic system, with systemic drainage to the inferior vena cava via an inferior mesenteric vein shunt. The cavoportal anastomosis remains patent with hepatopetal flow. Of the 12 previously reported cases of pediatric cavoportal hemitransposition as portal inflow in liver transplantation, this is the longest‐known follow‐up with a viable allograft. Notably, sequelae of portal hypertension were also rare in the 12 previously reported cases, with no cases of long‐term renal dysfunction, lower extremity edema, or ascites. Conclusions: Long‐term survival beyond 10 years with normal graft function is feasible following pediatric cavoportal hemitransposition. Complications related to portal hypertension were generally short‐lived, likely due to the development of robust collateral circulation. Additional reports of long‐term outcomes are necessary to facilitate informed decision making when considering pediatric cavoportal hemitransposition for liver graft inflow. [ABSTRACT FROM AUTHOR]

Background: Small‐for‐size syndrome (SFSS) in pediatric liver transplant recipients, particularly those weighing less than 10 kg, is rare. This report describes a case of a 15‐month‐old whole liver transplant recipient who suffered SFSS, and systematic literature review was performed to identify outcomes of such cases and potential risk factors for SFSS. Case Presentation: A 15‐month‐old toddler with a history of biliary atresia underwent a deceased donor whole liver transplant. The graft weighed 160 g, resulting in a graft‐to‐recipient weight ratio (GRWR) of 1.6%. The post‐operative course was complicated by SFSS, characterized by massive ascites causing hemodynamic instability and compromised hepatic artery flow. Pharmacological intervention with octreotide was initiated, and the patient eventually recovered. Conclusion: In small pediatric recipients, especially those weighing less than 10 kg, the native liver body weight ratio (LBWR) is significantly higher. When selecting an appropriately sized graft for these recipients, this higher ratio should be taken into consideration. The literature review suggests that a GRWR of less than 2% is associated with a higher incidence of small‐for‐size syndrome in small pediatric recipients weighing less than 10 kg. [ABSTRACT FROM AUTHOR]

Background: Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic. Methods: Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra‐ and postoperative course and overall survival (OS) were analyzed. Results: Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1–192 months), 60.5 (range: 1–215 months), 58.5 (range: 14–131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs. Conclusion: Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential. [ABSTRACT FROM AUTHOR]

Background: Liver transplant is the cure for children with liver failure. Sri Lanka is a lower‐middle‐income country with a predominant free, state health system. Pediatric liver transplant program in Sri Lanka is still in the budding state where the initial experience of the program is yet to be documented. Methods: A retrospective review was performed including the clinical characteristics of all pediatric liver transplant recipients of Colombo North Centre for Liver Diseases since the inception of the program from June 2020 to May 2023. Results: There were 14 PLT performed in 3 years. The median recipient age and weight were 8 years (6 months–15 years) and 23.3 kg (6.4–49.2), respectively. The majority were boys (64%). All were from low‐income backgrounds. Indications for LT were acute liver failure (5/14), decompensated chronic liver disease (5/14), and acute on chronic liver failure (4/14). Underlying liver diseases were Wilson disease (6/14), autoimmune liver disease (3/14), biliary atresia (2/14) and progressive familial intrahepatic cholestasis type 3 (1/14), and unknown etiology (2/14). The majority were living donor liver transplants (86%). Of the living donors, 42% (5/12) were Buddhist priests. There were three immediate deaths and two late deaths. The 3‐month survival was 78%, and overall survival was 64%. Living donor transplants carried a higher success rate (92%) compared to diseased donor transplants (0%; 2/2). Conclusions: Initial experience of pediatric liver transplant program of Sri Lanka is promising despite being established in a free healthcare system amidst the crisis circumstances. Initial experience of pediatric liver transplant program of Sri Lanka is promising despite being established in a free healthcare system amidst the crisis circumstances. There were 14 PLT performed in 3 years. [ABSTRACT FROM AUTHOR]

Introduction: Liver transplantation (LT) has emerged as a lifesaving modality for many liver diseases in children. Pediatric LT is an established treatment in the Western world but is relatively a new procedure in resource‐limited countries like Pakistan. The study aims to highlight the outcomes and survival of pediatric recipients from the first pediatric liver transplant center in Pakistan. Method: A retrospective analysis of pediatric LT was done from 2012 to 2019. The study was conducted in the Hepatobiliary and liver transplant department of Shifa International Hospital (SIH), Islamabad. A detailed analysis for indications for pediatric LT, survival, and complications was done. Results: Forty‐five patients under 18 years of age underwent Living donor liver transplant (LDLT) in SIH. Median age was 9 years and M:F of 2:1. Cryptogenic liver disease followed by Wilson disease were the two most common indications of LT. The majority of patients had chronic liver disease 34 (75%) while 11 (24%) had acute liver failure. The right lobe graft was the most common type of graft 19 (42.2%). Thirty days, 1‐year, 3‐year, and 5‐year survival was 77.8%, 75.6%, 73.3%, and 60.6% respectively. Mortality was highest in patients with biliary atresia 4 (33%). Causes of death included pulmonary embolism, sepsis, surgical complications, and acute kidney injury. Mean survival was 88.850 months (±7.899) (CI 73.369–104.331). Conclusion: Pediatric LDLT has offered disease‐free survival for patients. Survival can improve further with nutritional rehabilitation and anticipation and management of post‐operative complications. [ABSTRACT FROM AUTHOR]

Orthotopic liver transplantation (OLT) in the care of children with inborn errors of metabolism (IEM) is well established and represent the second most common indication for pediatric liver transplantation in most centers worldwide, behind biliary atresia. OLT offers cure of disease when a metabolic defect is confined to the liver, but may still be transformative on a patient's quality of life reducing the chance of metabolic crises causing neurological damage in children be with extrahepatic involvement and no "functional cure." Outcomes post‐OLT for inborn errors of metabolism are generally excellent. However, this benefit must be balanced with consideration of a composite risk of morbidity, and commitment to a lifetime of post‐transplant chronic disease management. An increasing number of transplant referrals for children with IEM has contributed to strain on graft access in many parts of the world. Pragmatic evaluation of IEM referrals is essential, particularly pertinent in cases where progression of extra‐hepatic disease is anticipated, with long‐term outcome expected to be poor. Decision to proceed with liver transplantation is highly individualized based on the child's dynamic risk‐benefit profile, their family unit, and their treating multidisciplinary team. Also to be considered is the chance of future treatments, such as gene therapies, emerging in the medium term. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) is a serious cardiovascular stressor for patients with end‐stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. Methods: A total of 1005 patients were included in this study. The Kaplan–Meier method with log‐rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. Results: The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no‐CHD group (13.2% vs. 5.0%, p =.045 and 15.8% vs. 6.2%, p =.019, respectively). The 5‐year patient survival and graft survival in the CHD group versus the no‐CHD group was 86.8% versus 94.7% (log‐rank p =.022) and 84.2% versus 93.5% (log‐rank p =.015), respectively. No significant differences were observed in re‐transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. Conclusion: The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT. [ABSTRACT FROM AUTHOR]

A 15‐year‐old girl with recurrent upper abdominal pain was diagnosed with congenital biliary dilatation. Abdominal enhanced computed tomography (CT) showed the anterior segmental branch of the right hepatic artery (RHA) running across the ventral aspect of the dilated common hepatic duct (CHD). Laparoscopic extrahepatic dilated biliary duct excision and Roux‐en‐Y hepaticojejunostomy were planned. Intraoperatively, the dilated CHD was observed to bifurcate into the ventral and dorsal ducts, between which the anterior segmental branch of the RHA crossed through the CHD. The CHD rejoined on the distal side as one duct. We transected the CHD just above the cystic duct. The patency of the ventral and dorsal sides of the bifurcated CHD was confirmed. Laparoscopic hepaticojejunostomy was performed at the distal side of the rejoined CHD, without sacrificing the anterior segmental branch of the RHA. There was no postoperative blood flow impairment in the right hepatic lobe or anastomotic stenosis. [ABSTRACT FROM AUTHOR]

Background: Post‐COVID‐19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID‐19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post‐COVID‐19 cholangiopathy. Methods: Seven patients who underwent liver transplantation for post‐COVID‐19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi‐center case series. Results: At the time of initial COVID‐19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID‐19 diagnosis to the diagnosis of post‐COVID‐19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10–38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow‐up of 11 months. Conclusions: Liver transplantation is a viable option for patients with post‐COVID‐19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is rare liver disease of unknown etiology, and is a major indication for liver transplant (LT). Previous data indicate improved outcomes with early referral for Kasai portoenterostomy (KPE). Objective: Evaluate the long‐term outcomes in BA, with particular focus on those transitioned to adult care with native livers. Subjects and Methods: Patients with BA treated between1980 and 2012 were identified. Data were collected from the time of referral, transition to adult care, and the most recent clinic notes, from which patient and native liver survival were calculated. Results: Four hundred and fifty‐four patients with BA were identified, who were followed up for median of 16.4 years from birth; 74 died (41 of whom had a LT), giving a 20‐year survival rate of 83.6%. Two hundred and seventy‐two patients received an LT, with the median native liver survival being 35 months. Of patients who transitioned to adult care, 54 of 180 (30.0%) retained their native liver. Of these, 72% (39 of 54) had evidence of chronic liver disease at transition, of whom 8 were subsequently lost to follow‐up, 9 were transplanted, and 22 remained stable with compensated liver disease. Of the 15 of 54 patients (28%) with no evidence of chronic disease in their native liver disease at transition, 3 were subsequently lost to follow‐up; none received transplants, although 3 patients developed new‐onset liver disease. All patients transitioned to adult care completed secondary school education (N = 180), with 49% having attended college/university and 87% being in employment or education at the last follow‐up. Of female patients, 34% had at least one pregnancy (27 children in 21 women), while 22% of males had fathered a child. Conclusion: Long‐term outcomes in BA are good, with patients surviving into adult life. Progression of chronic liver disease and associated morbidity is common in those who retained their native livers, suggesting that these patients require monitoring of liver disease throughout adult life, and early recognition of the need for LT. [ABSTRACT FROM AUTHOR]

Aims: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene‐clinical model based on two‐dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. Methods: Differentially expressed gene patterns between liver samples of BA (n = 102) and non‐BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C‐index. Results: Using the least absolute shrinkage and selection operator model, we generated a nine‐gene prognostic classifier. The nomogram based on the nine‐gene classifier, age, preoperative 2DSWE, and albumin had the better C‐index compared to gene classifier alone in the training cohort (0.83 [0.76–0.90] vs. 0.69 [0.61–0.77], p = 0.003) and the validation cohort (0.74 [0.67–0.82] vs. 0.62 [0.55–0.70], p = 0.001). Using risk scores developed from the nomogram, the 12‐month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7–56.3) in the high‐risk group and 80.8% (95% CI, 63.4–100.0) in the low‐risk group in the validation cohort. Conclusions: The comprehensive genetic‐clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE. [ABSTRACT FROM AUTHOR]

Aim: The etiology of non‐syndromic biliary atresia (BA) remains largely unknown. In this study, we performed genome‐wide screening of genes associated with the risk of non‐syndromic BA. Methods: We analyzed exome data of 15 Japanese patients with non‐syndromic BA and 509 control individuals using an optimal sequence kernel association test (SKAT‐O), a gene‐based association study optimized for small‐number subjects. Furthermore, we examined the frequencies of known BA‐related single‐nucleotide polymorphisms in the BA and control groups. Results: SKAT‐O showed that rare damaging variants of MFHAS1, a ubiquitously expressed gene encoding a Toll‐like receptor‐associated protein, were more common in the BA group than in the control group (Bonferroni corrected p‐value = 0.0097). Specifically, p.Val106Gly and p.Arg556Cys significantly accumulated in the patient group. These variants resided within functionally important domains. SKAT‐O excluded the presence of other genes significantly associated with the disease risk. Of 60 known BA‐associated single‐nucleotide polymorphisms, only eight were identified in the BA group. In particular, p.Ile3421Met of MYO15A and p.Ala421Thr of THOC2 were more common in the BA group than in the control group. However, the significance of these two variants is questionable, because MYO15A has been linked to deafness, but not to BA, and the p.Ala421Thr of THOC2 represents a relatively common single‐nucleotide polymorphism in Asia. Conclusions: The results of this study indicate that rare damaging variants in MFHAS1 may constitute a risk factor for non‐syndromic BA, whereas the contribution of other monogenic variants to the disease predisposition is limited. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) has been indicated for smaller and more clinically severe patients in recent years. Small biliary atresia (BA) patients often show portal hypoplasia and sclerotic portal vein (PV), which may make PV reconstruction more difficult during the operation. Among PV complications, intraoperative PV thrombosis can be considered a disaster, and it is important to prevent this catastrophic event by the precise assessment of the PV structure and PVF using radiological imaging before and during LT. However, there are no objective parameters to indicate whether sufficient PVF can be obtained. PV pressure (PVP) and PV flow (PVF) have mainly been studied in adult living donor LT, for the purpose of preventing small‐for‐size syndrome, and PVP has been considered an objective parameter of graft inflow modulation (GIM). In the setting of pediatric LT, GIM is mainly performed to prevent hypoperfusion, and it must be performed before graft implantation. GIM to maximize the PVF of pediatric patients with potentially low PVF in LT consists of the interruption of collateral vessels, the assessment of the usability of the native PV, and technical modifications in PV reconstruction. Reliable objective parameters that represent sufficient PVF before graft implantation are desired. Our recent study proposed that a PVP of ≥25 mmHg before graft implantation can be considered an objective parameter to obtain sufficient PVF (cutoff value: 50 mL/min/100 g of graft weight). Further investigation is needed to determine the best strategy for successful PV reconstruction in pediatric LT. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A newborn with a rare form of biliary atresia had posterior fossa bleed and subarachnoid hemorrhage despite vitamin K prophylaxis, indicating biliary atresia is a causality rather than chance. Biliary atresia frequently causes surgical jaundice, resulting in delayed vitamin K deficiency. We report a 28‐day‐old newborn diagnosed with a rare form of biliary atresia presented with an unusual association of posterior fossa bleed and subarachnoid hemorrhage despite vitamin K prophylaxis. Thus, biliary atresia remains causality rather than chance. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. Methods: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non‐BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing‐risk regression analysis, graft survival rates were compared using Kaplan–Meier time‐to‐event analysis and Cox proportional hazards modelling provided adjusted estimates. Results: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non‐BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living‐donor liver transplantations (LDLT) and 611 (27.7%) split deceased‐donor LTs. Five‐year graft survival was significantly higher among BA versus non‐BA cholestatic patients in the older group (88.3% vs. 79.5%, p <.01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03–3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87–6.2). Conclusion: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes. [ABSTRACT FROM AUTHOR]

Aim: The gut–liver axis may contribute to pathophysiology of cholestatic liver disorders like biliary atresia (BA) by bacterial translocation (BT). Toll‐like receptors (TLR) are pattern recognition receptors known to activate innate immunity and secretion of inflammatory cytokines. Herein, we examined BT‐associated biomarkers and TLRs in relation to liver injury after successful portoenterostomy (SPE) in BA. Methods: Serum levels of lipopolysaccharide‐binding protein (LBP), CD14, LAL, TNF‐α, IL‐6 and FABP2 along with liver expression of TLRs (TLR1, TLR4, TLR7 and TLR9), LBP and CD14 were measured during median 4.9 (1.7–10.6) years follow‐up after SPE in 45 BA patients. Results: Serum LBP, CD14, TNF‐α and IL‐6 all increased after SPE whereas LAL and FABP‐2 remained unchanged. Serum LBP correlated positively with CD14 and markers of hepatocyte injury and cholestasis, but not with Metavir fibrosis stage, transcriptional markers for fibrosis (ACTA2) or ductular reaction. Serum CD14 concentration was significantly higher in patients with portal hypertension than without. While liver expression of TLR4 and LBP remained low, TLR7 and TLR1 showed marked BA‐specific increases, and TLR7 correlated with Metavir fibrosis stage and ACTA2. Conclusion: BT does not seem to play a significant role in liver injury after SPE in our series of BA patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Several studies describe poorer motor developmental motor outcomes post‐liver transplant (LT) in younger children. Limited studies examine physical function in older children and adolescents pre‐ and post‐LT. Methods: Retrospective review of standard of care physical function outcome measures pre‐ and 1‐year post‐LT in children ≥6 years at LT. Measures include: 6‐minute walk test (6MWT), grip strength, Bruininks‐Oseretsky Test of Motor Proficiency‐2 (BOT‐2) components, Physical Activity Questionnaire (PAQ), and Paediatric Quality of Life Multidimensional Fatigue Scale. Association of medical variables with outcomes was explored. Results: The study cohort included 23 (8 male, median (interquartile range) age 11.67 (8.25, 13.92) years at LT) participants. Top two primary diagnoses included biliary atresia (30.4%) and fulminant hepatic failure (21.7%). At 1‐year post‐LT, over one‐third (36%) were overweight or obese. Compared with healthy norms, children had significantly lower pre‐LT PAQ scores (p =.002), pre‐ and post‐6MWT scores (p <.001) and post‐LT BOT‐2 strength and agility scores (p <.001). Pre‐LT, lower balance scores were associated with abdominal distention/ascites (p =.009) and splenomegaly (p =.017). Lower pre‐LT platelet count correlated with poorer balance (r =.532, p =.017) and lower strength and agility scores (r =.446, p =.043). Significant moderate inverse correlations were found between weight/body mass index z‐scores and BOT‐2 components. Post‐LT children continue to demonstrate decreased levels of motor proficiency and functional capacity but report less fatigue and increased physical activity. Conclusions: Older children and adolescents undergoing LT are at risk of decreased physical function, highlighting the need for pre‐ and post‐LT rehabilitation to optimize long term outcomes. [ABSTRACT FROM AUTHOR]

Key Clinical Message: ERCP is a safe and effective method for managing biliary obstruction in children. A case report illustrates successful removal of a bile duct stone in a 5‐year‐old child using ERCP. Pediatric ERCP is a viable option for treating biliary diseases in well‐equipped centers, alongside other approaches. We describe a 5‐year‐old child with extrahepatic biliary stone who successfully underwent endoscopic retrograde cholangiopancreatography for stone removal. He suffered from persistent colicky abdominal pain accompanied by fever that confirmed biliary stone. ERCP along with other methods, can be considered a safe procedure for managing BD in children. [ABSTRACT FROM AUTHOR]

This article discusses the condition known as parenteral nutrition-associated cholestasis (PNAC) in preterm infants. PNAC is a liver disease that can occur as a result of receiving parenteral nutrition, a medical treatment for infants. The article explores the risk factors for PNAC and the dynamics of biochemical liver markers in affected infants. It also highlights the importance of understanding the natural course of PNAC to prevent unnecessary invasive examinations. The study found that cholestasis can persist for several weeks after the cessation of parenteral nutrition and that elevated liver transaminases may persist even longer. The article concludes by emphasizing the need for individual assessment and non-invasive evaluations to determine the cause of cholestasis in preterm infants. [Extracted from the article]

This case report highlights the investigation and treatment of a 70‐year‐old male with cytomegalovirus (CMV) cholangiopathy. The patient underwent a kidney transplant in 2016 and presented 3 years later with the atypical presentation of left shoulder pain associated with dilated biliary tree and mild transaminitis. Initial endoscopic retrograde cholangiopancreatography (ERCP) showed diffuse stricture of the common bile duct, requiring stenting, and over the course of a year multiple stent changes were required to prevent cholestasis. CMV polymerase chain reaction (PCR) tests were conducted on bile duct brushings and found to be positive. Oral valganciclovir was given for 6 weeks but the strictures did not resolve. He underwent a laparoscopic total choledochectomy and hepaticojejunostomy as definitive treatment. CMV involvement of the biliary tract has rarely been reported in kidney transplant patients. Antiviral therapy in the form of ganciclovir or valganciclovir is often sufficient to eradicate CMV infection and improve clinical disease. Surgical management should be considered only if the patient has failed medical therapy, or if there is suspicion of malignancy. This case shows that in renal transplant patients presenting with cholangiopathy, CMV disease should be considered as a possible differential even in patients without early CMV infection or with prior CMV prophylaxis. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a rare but devastating cholangiopathy. We report a case series of dysmorphic gallbladders detected during prenatal ultrasound, which were confirmed as BA after birth. We present the prenatal ultrasound findings as well as integral follow‐up, with an aim to raise awareness regarding the association between BA and dysmorphic gallbladder. Although this dysmorphic gallbladder is a strong hint for BA, it is also important to search for other related sonographic features, such as the presence of microcysts at the hepatic hilum, dilated right hepatic artery, and seroperitoneum, which may provide more evidence for the diagnosis of BA. [ABSTRACT FROM AUTHOR]

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein‐altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child–parent trios, one child–mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio‐based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case–control analysis using a sequence kernel‐based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is an endothelial cell tumor, rare in children. It is 200 times more frequent after solid organ transplantation than in the general population. Methods: We report three cases of pediatric patients who developed KS after liver transplantation (LT). Results: Case 1, a 4‐year‐old boy undergoing LT due to familial intrahepatic cholestasis. Five months after LT, he presented with fever, dyspnea, and cough with enlarged lymph nodes and splenomegaly, anemia, thrombocytopenia, elevated liver enzymes, and positive EBV viral load. Lymph node biopsy diagnosed KS with an elevated HHV8 viral load. Case 2, a 4‐year‐old boy who underwent LT due to secondary biliary cirrhosis resulting from extrahepatic biliary atresia. Two years later, graft dysfunction was noticed with positive EBV viral load, thrombocytopenia, massive cervical lymph node enlargement, and splenomegaly. Lymph node biopsy diagnosed KS, Castleman's disease, and plasmablastic lymphoma related to HHV8 infection. Case 3, a 15‐month‐old girl, who received two LT due to biliary cirrhosis. Six months later, she presented with diarrhea, abdominal distension, anemia, thrombocytopenia, enlarged lymph nodes, splenomegaly, and positive CMV viral load. Axillary lymph node biopsy diagnosed KS and HHV8 infection was confirmed. In all three cases, tacrolimus was discontinued and, after diagnosis, sirolimus was started. All recovered without relapse and have a good graft function. Conclusions: Kaposi sarcoma is a rare disease post‐LT in children. Recognizing keywords and early diagnosis is crucial for timely treatment and survival. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present the case of a rare obstetric emergency, which is usually fatal. Our case highlights suspicion of AFLP in patients presenting with jaundice in the third trimester with good maternal and fetal outcomes after a timely intervention. Acute fatty liver of pregnancy (AFLP) is a rare, obstetric emergency characterized by maternal liver dysfunction that can lead to maternal and fetal complications. We report a case of 28‐year‐old primigravida 39 weeks gestation diagnosed with AFLP complicated by coagulopathy with good maternal and fetal outcomes after a timely intervention. [ABSTRACT FROM AUTHOR]

Bile lake, of the postoperative complications after Kasai portoenterostomy (PE) for biliary atresia, causes cholangitis that may induce progressive fibrosis of the liver. Standard treatment for bile lakes has not yet been established, but there are reports that surgical internal intestinal drainage for bile lakes effectively prevents cholangitis and maintains jaundice‐free status. In this case, insertion of the percutaneous transhepatic biliary drainage into the bile lake allowed continuous drainage of large volumes of bile juice. However, reoperation following laparotomy increases the surgical risk of subsequent liver transplantation due to postoperative adhesion. Laparoscopic surgery was selected for the patient who was likely to require liver transplantation in the future. In this case, laparoscopic internal intestinal drainage of bile lakes was performed safely by a Cavitron ultrasonic surgical aspirator for the recurrence of jaundice after laparoscopic revision of PE. Cholangitis and jaundice were rapidly resolved after this surgical procedure. [ABSTRACT FROM AUTHOR]

Cholestasis is a main clinical feature of biliary atresia (BA), which leads to liver fibrosis (LF). The focus of BA treatment is preventing and slowing the progress of LF. This study reports the improvement effect of anlotinib on common bile duct ligature (BDL)‐induced LF in young rats. The BDL young rats were treated with anlotinib and the serum levels of aspartate aminotransferase, alanine aminotransferase, albumin, and total bilirubin were determined. Histological staining was performed and pathological changes in liver tissue were observed. The expression levels of α‐SMA, collagen I, CD31, TGF‐β1, phospho‐VEGFR2, phospho‐4E/BP1, and phospho‐S6K1 were determined. The results showed that anlotinib significantly improved the liver function and histopathological injury of BDL rats, inhibited the deposition of collagen and hepatocyte apoptosis, and downregulated the protein expression of α‐SMA and collagen I. Furthermore, anlotinib treatment significantly inhibited microvascular formation in the liver and downregulated the expression level of phospho‐VEGFR2, thereby suggesting that the antifibrosis effect of anlotinib may be achieved by antiangiogenesis. In addition, anlotinib downregulated the expression of phospho‐S6K1 and upregulated the expression of phospho‐4E/BP1, two downstream proteins of the mammalian target of rapamycin (mTOR) pathway. MHY1485, an agonist of mTOR, significantly reversed the inhibitory effect of anlotinib on angiogenesis and LF but did not influence the effect of anlotinib on the downregulation of phospho‐VEGFR2 expression. Together, the above‐mentioned results suggest that the effect of anlotinib on BDL‐induced LF involves at least antiangiogenesis regulated by the VEGFR2/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Aims: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post‐transplantation. Methods: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense‐sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. Results: Disposition of tacrolimus was best characterized by a 2‐compartment model with clearance achieving half of the maximum elimination capacity (CLMAX = 4.1 L/h) at 4.6 days post‐transplantation (T50). Compared to sedated patients, nonsedated status showed an increased first‐order absorption rate constant (1.1 vs. 0.1 h−1) and a 24% reduction in bioavailability (FNS) at 14 days post‐transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first‐pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50). Conclusion: A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post‐transplant time on clearance and the sedation status may be considered in routine dosing management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Biliary atresia is a rare obstructive cholangiopathy that presents in infants. The Kasai portoenterostomy procedure, which reestablishes biliary drainage into the intestine, is a surgical procedure that has been found to improve survival with the native liver. The options for postoperative analgesia include systemic opioids and epidural analgesia. The primary objective of this study was to compare the postoperative systemic opioids used in morphine equivalents (mg/kg) on postoperative days 0 through 3 between patients who underwent a Kasai portoenterostomy and received a thoracic epidural infusion to those without thoracic epidural analgesia. Methods: We conducted a retrospective cohort study of 91 infants with biliary atresia undergoing a Kasai portoenterostomy between January 1, 2009, and September 1, 2019, at the Children's Hospital of Philadelphia. Results: Sixty‐three of the 91 patients (69%) had a continuous epidural catheter placed intraoperatively for postoperative analgesia. The total opioid requirement (morphine equivalents) for the first 72 h in the epidural group of (Mean (95% confidence interval): 0.52 mg/kg (0.38, 0.67 mg/kg) was lower than the non‐epidural group (Mean (95% confidence interval): 1.15 mg/kg (0.8, 1.48 mg//kg) for a difference in mean opioid requirement (95% confidence interval) of 0.63 mg/kg (0.32, 0.94 mg/kg). Patients in the non‐epidural group had higher rates of unplanned ICU admissions (36% non‐epidural group vs. 3.3% epidural group, difference in proportion (95% confidence interval) 32.7% (13, 52%), p <.01). A higher percentage of patients in the non‐epidural group had a postoperative oxygen requirement (32.1% vs. 11.3%, difference in proportion (95% confidence interval) 21% (2, 40%), p =.02). Conclusion: In our cohort study, continuous thoracic epidural analgesia in patients undergoing a Kasai portoenterostomy was associated with lower postoperative opioid use. We also observed that the epidural group had a lower ICU admission rate and a lower rate of postoperative supplemental oxygen requirement over the first three postoperative days. [ABSTRACT FROM AUTHOR]

Background: Esophagogastric varices (EGVs) may develop as a result of portal hypertension in children with biliary atresia (BA). Although endoscopic injection sclerotherapy (EIS) with ethanolamine oleate (EO) is reported useful for children, risk factors associated with the presence of high‐risk EGVs after treatment remain unknown. Methods: The subjects were BA patients under 15 years of age who underwent EO‐EIS. We retrospectively reviewed a total of 28 treatment sessions of EGVs with red signs and those larger than F2, which were considered to be at high risk of bleeding. Survival analysis was performed for the presence of high‐risk EGVs at the time of follow‐up endoscopy as the occurrence of an event. Results: Univariate analysis showed a significantly increased risk of the presence of high‐risk EGVs post‐EO‐EIS in patients with increased liver stiffness (LS) and Mac‐2 binding protein glycan isomer (M2BPGi), with hazard ratios of 1.48 and 1.15, respectively. The median presence‐free period was significantly shorter in the LS ≥ 2.8 m/s patients than in those with LS <2.8 m/s (189 vs. 266 days). Similarly, the median presence‐free period was significantly shorter in patients with M2BPGi ≥ 4.0 than in those with M2BPGi < 4.0 (182 vs. 203 days). The results of multivariate analysis revealed that the risk of the presence of high‐risk EGVs was significantly higher only in the high‐LS group, with a hazard ratio of 2.76. Conclusions: Increased LS is associated with risk of the presence of high‐risk EGVs following EO‐EIS in children with BA. [ABSTRACT FROM AUTHOR]

Background: Repeat liver transplantation (LT) for patients with the liver graft failure who underwent metallic stent placement in the previous graft hepatic vein (HV) for HV complications can be very difficult. We retrospectively reviewed the safer surgical procedures during repeat LT for patients with a metallic stent in the graft HV. Case Reports: Patient 1 with biliary atresia who was treated with metallic stent placement for HV stenosis underwent a third LT form a deceased donor at the age 17 years. Patient 2 with ornithine transcarbamylase deficiency who was treated with metallic stent placement for refractory HV stenosis underwent a second LT form a deceased donor at age 9 years. In both patients, transection of the previous graft HV through an intraabdominal approach was difficult during repeat LT, and a supradiaphragmatic inferior vena cava (IVC) approach was introduced. Using a midline incision of the diaphragm, the pericardium was incised and the supradiaphragmatic IVC was encircled. After clamping the supradiaphragmatic IVC, graft hepatectomy was performed. The metallic stent was successfully removed breaking, and HV reconstruction was performed on the suprahepatic IVC. Both patients did well without serious HV complications after repeat LT. Conclusions: The surgical technique for the supradiaphragmatic IVC approach is useful to decrease the risk of fatal operative complications during repeat LT for patients with a metallic stent in the graft HV. [ABSTRACT FROM AUTHOR]

Background and Aims: Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK‐cell modulator. Here, we explored the role of PVR in BA pathogenesis. Methods: Poliovirus receptor expression and NK cell‐associated genes were detected in human BA samples and a rotavirus‐induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK‐cell‐mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high‐mobility group box 1 (HMGB1), and interleukin‐1beta (IL‐1beta) levels were measured in a cohort of 50 patients using ELISA. Results: Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus‐induced BA. Activation of the TLR3‐IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell‐mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL‐1beta levels. Conclusions: Poliovirus receptor contributes to BA pathogenesis by regulating NK cell‐mediated bile duct injury; PVR has the value as a biomarker of BA. [ABSTRACT FROM AUTHOR]

Background and Aim: Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in biliary atresia (BA). Methods: We report the clinical characteristics, outcomes, and genetic mutations of 25 children with ALGS followed for a median of 7.3 years. Patients were classified into (i) jaundice‐free (JF) group (resolving jaundice after 2 years of age); (ii) progressive disease (PD) group (persistent jaundice or progressive cholestasis). In addition, we analyzed the explant liver in 10 ALGS patients compared with 20 age‐matched BA patients at the time of LT. Results: Nine patients (36%) in the JF group had a favorable outcome, with longer native liver survival than patients with PD (n = 16, P < 0.001). Fourteen of the PD group patients received LT or died. We identified 18 different JAG1 mutations in 22 patients. Three unrelated probands in the JF group had the same de novo mutation in JAG1, c.2122‐2125delCAGT. Compared with BA children, ALGS patients had lower METAVIR scores in liver pathology, higher serum albumin levels, and lower weight‐for‐age z‐scores when receiving LT. Conclusion: One‐third of ALGS patients had JF and a favorable course. Children with ALGS presenting with persistent jaundice beyond 2 years of age should be cautioned for poor prognosis. ALGS patients tend to have a lesser extent of cirrhosis, and more growth problems than BA patients at the time of LT. [ABSTRACT FROM AUTHOR]

Background: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes. Methods: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019. Results: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole‐liver‐transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow‐up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss. Conclusions: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is a devastating inflammatory and fibrosing cholangiopathy of neonates with unknown aetiology. We aim to investigate the relationship between these two main characteristics. Methods: Single‐cell RNA sequencing and spatial transcriptomics were performed on liver samples from a cohort of 14 objects (BA: n = 6; control: n = 8). We conducted data integration and cell‐type annotation based on gene expression profiling. Furthermore, we identified fibrosis‐related immune cells according to their spatial locations, GO and KEGG analysis. Finally, SPOTlight and CIBERSORTx were used to deconvolute ST data and microarray data of the GSE46960 cohorts, respectively. Results: Immune subpopulations inhabiting the 'fibrotic niche' (areas of scarring), comprising 'intermediate' CD14++CD16+ monocytes, scar‐associated macrophages, natural killer T cells, transitional B cells and FCN3+ neutrophils were identified. GO and KEGG analyses showed that pathways including 'positive regulation of smooth muscle cell/fibroblast proliferation' and 'positive regulation of/response to VEGFR/VEGF/EGFR/FGF' were enriched in these cell types. Interactions analysis showed that communication among 'FGF_FGFR', 'RPS19‐C5AR1', 'CD74_COPA/MIF/APP' and 'TNFRSF1A/B_GRN' was extensive. Finally, the results of deconvolution for ST data and microarray data validated that the proportions of certain identified fibrosis‐related cell types we identified were increased in BA. Discussion: Fibrosis is an important feature of BA, in which the immune system plays an important role. Our work reveals the subpopulations of immune cells enriched in the fibrotic niche of BA liver, as well as key related pathways and molecules; some are highlighted for the first time in liver fibrosis. These newly identified interactions might partly explain why the rate of liver fibrosis occurs much faster in BA than in other liver diseases. Conclusion: Our study revealed the molecular, cellular and spatial immune microenvironment of the fibrotic niche of BA. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a biliary atresia (BA) diagnostic score based on serum gamma‐glutamyl transferase (GGT) levels and conventional ultrasound features for discriminating BA in patients with jaundice from two centers. Methods: A total of 958 patients from one hospital were classified as the derivation cohort, and 725 patients from another hospital were classified as the validation cohort. The optimal GGT cutoff value for diagnosing BA was calculated in the derivation cohort and subsequently verified in the validation cohort. Gallbladder abnormalities and the triangular cord (TC) sign were evaluated in all patients. A BA diagnostic score was developed for diagnosing BA using the GGT levels, gallbladder abnormalities and the TC sign based on the data from the derivation cohort followed by external validation. Results: Based on the optimal cutoff value 350.0 U/L, GGT yielded a sensitivity of 59.3% and specificity of 85.4% in diagnosing BA. The area under the receiver operating characteristic curve (AUC 0.724) was inferior to that of the gallbladder (AUC 0.911, P <.001) and comparable to that of the TC sign (AUC 0.771, P =.128). The combination of GGT and ultrasound diagnosis could help to reduce the misdiagnosis of 9 infants with BA. The BA diagnostic score yielded a sensitivity of 93.3% and specificity of 95.0% with the highest AUC in this study (0.941). Conclusions: GGT can add diagnostic value to ultrasound examination when diagnosing BA. The BA diagnostic score based on GGT, gallbladder abnormalities and the TC sign shows satisfactory discrimination abilities in BA. [ABSTRACT FROM AUTHOR]

This article explores the use of prenatal ultrasound in diagnosing biliary atresia (BA) and analyzing its prognostic implications. The study included 45,020 cases, with 359 cases suspected to have biliary abnormalities. Postpartum diagnosis confirmed BA in 14 cases, with significant differences observed in cyst size, shape, cystic changes, and gallbladder morphology between BA and biliary dilatation groups. The prognosis for biliary atresia splenic malformation syndrome was generally unfavorable, while those undergoing surgery had favorable outcomes. The study provides valuable information for clinical decision-making regarding BA. [Extracted from the article]