Search

Background: Systemic Immune-Inflammation Index (SII), known as an easy, economical and useful marker, correlates with the balance of inflammation and immune response. However, the usefulness of SII in biliary atresia (BA) remains unclear. Therefore, we evaluated the relationship of SII level and postoperative clinical outcomes of BA. Methods: Retrospective review of 168 patients with BA was conducted with assessments of demographic information, histological findings, laboratory parameters, and clinical outcomes. The LASSO logistic regression analysis was established using the "glmnet" software package to explore the influencing factors related to native liver survival time. Numerical variables were dichotomized based on the receiver operating characteristic (ROC) curve and Youden index yielding the best performance of prediction. R software was used for statistical analysis. Results: Overall, the 24 month native liver survival rate was 43.5% (73 cases) after Kasai portoenterostomy. LASSO logistic regression analysis show that preoperative malnutrition (OR = 0.032, 95%CI 0.001–0.424), gamma-glutamyltransferase (GGT, OR = 0.994, 95%CI 0.987–0.998), lymphocyte count (LY, OR = 2.426, 95%CI 1.467–4.604), SII (OR = 0.977, 95%CI 0.960–0.989), and liver fibrosis grading (LFG, reference: Grade 1, Grade 3, OR = 0.076, 95%CI 0.007–0.614) were the independent influencing factors for 24 month native liver survival. ROC curve analysis showed that the area under the curve of SII level (0.919) was larger than that of preoperative malnutrition (0.690), LFG (0.759), GGT (0.747), and Ly (0.773). A SII < 140.09 was found to be a significant marker in the prediction of 24-month native liver survival, with 90.41% sensitivity and 93.68% specificity. Furthermore, the rates of 24-month native liver survival (33.1% vs. 72.7%), jaundice clearance (46.8% vs. 75.0%), and good liver function recovery (46.8% vs. 65.9%) were lower in the SII ≥ 140.09 group than that in the SII < 140.09 group (all P < 0.05), but there was no difference in the occurrence of cholangitis (P > 0.05). Conclusion: Preoperative malnutrition, GGT, Ly, SII, and LFG were independent influencing factors for postoperative 24-month native liver survival of BA. The SII level, as a routine haematological marker, has better universality and simplicity and is related to clinical outcomes after Kasai portoenterostomy. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates the presence of vascular abnormalities and ischemia in biliary atresia (BA), although specific mechanisms remain undefined. This study examined both human and experimental BA. Structural and hemodynamic features of hepatic arteries were investigated by Doppler ultrasound, indocyanine green angiography, microscopic histology, and invasive arterial pressure measurement. Opal multiplex immunohistochemistry, western blot, and RT-PCR were applied to assess Notch3 expression and the phenotype of hepatic arterial smooth muscle cells (HASMCs). We established animal models of Notch3 inhibition, overexpression, and knockout to evaluate the differences in overall survival, hepatic artery morphology, peribiliary hypoxia, and HASMC phenotype. Hypertrophic hepatic arteriopathy was evidenced by an increased wall-to-lumen ratio and clinically manifested as hepatic arterial hypertension, decreased hepatic artery perfusion, and formation of hepatic subcapsular vascular plexuses (HSVPs). We observed a correlation between overactivation of Notch3 and phenotypic disruption of HASMCs with the exacerbation of peribiliary hypoxia. Notch3 signaling mediated the phenotype alteration of HASMCs, resulting in arterial wall thickening and impaired oxygen supply in the portal microenvironment. Inhibition of Notch3/Hey1 ameliorates portal hypoxia by restoring the balance of contractile/synthetic HASMCs, thereby preventing hypertrophic arteriopathy in BA. [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]

Background: Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. Methods: We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. Results: A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792–0.836) and specificity of 72.1% (95% CI 0.693–0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833–0.911) but lower specificity of 59.4% (95% CI 0.549–0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893–0.934) and a specificity of 84.3% (95% CI 0.820–0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549–0.613) and high specificity of 92.9% (95% CI 0.911–0.944). HS had a high sensitivity of 98.4% (95% CI 0.968–0.994) and moderate specificity of 79.0% (95% CI 0.762–0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900–1.000) and specificity of 87.0% (95% CI 0.767–0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. Conclusion: MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA. [ABSTRACT FROM AUTHOR]

Portopulmonary hypertension is an intractable form of pulmonary hypertension. Although liver transplantation is recommended for patients who respond poorly to treatments, the mechanisms by which liver transplantation improves pulmonary hypertension remain unclear. The present study investigated these mechanisms by retrospectively evaluating patients' data. This study retrospectively evaluated echocardiography and catheterization data before and after liver transplantation in 12 patients who underwent liver transplantation from 2001 to 2019. The 12 patients included one male and 11 females, of median age at liver transplantation of 10 years, 2 months. Nine patients underwent liver transplantation for congenital biliary atresia and three for portal vein aplasia or hypoplasia. Mean pulmonary arterial pressure was 44.1 ± 8.1 mmHg at the first cardiac catheter examination, 35.3 ± 7.8 mmHg before liver transplantation, and 29.5 ± 9.3 mmHg 6 months after liver transplantation. Pulmonary artery pressure was reduced by treatments of pulmonary hypertension and by liver transplantation. Pulmonary vascular resistance did not differ before and after liver transplantation, whereas the cardiac index decreased significantly, indicating that the significant reduction in mean pulmonary artery pressure was due to a decrease in cardiac index. Decreased cardiac index was thought to result from improvements in hyperdynamic conditions due to increased (normalized) systemic vascular resistance. Liver transplantation likely suppresses shear stress on pulmonary arteries, preventing further damage by hyper-circulation. A longer-term evaluation is required to determine the effect of improving pulmonary artery remodeling. [ABSTRACT FROM AUTHOR]

Background: It has been shown that hyperlipidemia occurs in 71% of patients following liver transplantation. Multiple risk factors, including obesity, diabetes mellitus, and diet, as well as the immunosuppressive medications used, influence the lipid profiles that are seen in these individuals, contributing to the multifactorial etiology of lipid problems. Objectives: The aim of the present study is to compare the lipid profile in liver transplant recipients from living-related (LR) and deceased donors (DDs). Methods: This is a retrospective cross-sectional study performed at Shiraz University of Medical Science between 2005 and 2018. Patients under 18 years old who received liver transplants were included in the study and divided into 2 groups who received from LR and DDs, and lipid profiles were compared between the 2 groups. Results: A total of 397 patients were included in the study; in the first group, 234 received a liver from a DD, and in the second group, 161 from an LR donor. The mean body mass index (BMI) was 17.51 ± 5.49 in the first group and 16.25 ± 3.29 in the second group. The most common underlying diseases were biliary atresia (22%) and autoimmune hepatitis (15%). The mean triglyceride (TG) and high-density lipoprotein (HDL) levels were 133 and 46 mg/dL in the first group and 118 and 54 mg/dL in the second group, while the differences were statistically significant. As age increased, there was a significant difference in the mean values of fasting blood sugar (FBS) and HDL, with FBS increasing and HDL decreasing. There was no significant difference in the use of immunosuppressant drugs between the 2 groups. Conclusions: Patients who received a liver from an LR donor have a significantly lower TG, higher HDL, and a lower cardiovascular risk. [ABSTRACT FROM AUTHOR]

Objective: Early diagnosis of biliary atresia (BA) and the timing of Kasai hepatic portoenterostomy are associated with improved survival rates of the native liver. Acholic stool is a major and earliest sign of BA. We evaluated the awareness and recognition of medical students and primary health care professionals (PHCPs) about neonatal cholestasis and acholic stool as a marker of BA. Materials and Methods: The knowledge of students and PHCP about prolonged jaundice and acholic stool was evaluated through a questionnaire. In the first step, 5 questions evaluating the knowledge of prolonged jaundice were asked. The sixth question was “Have you ever seen acholic stool before?” Following this question, stool color cards with 9 colors were shown, and participants were asked “Which of the following stool pictures would you define as acholic?” Results: A total 724 students and 88 PHCPs were included in the study. In both groups, about half of the participants could not answer the first 4questions related to prolonged jaundice and cholestasis correctly. Twenty-four percent of the students and 11.4% of PHCP answered correctly to all of the stool colors. The rate of correct answers to acholic stool colors were approximately 43.9%-87.6% and 23.9%-86.4% for students and PHCP, respectively. Whitish acholic stool colors were better known than mild yellowish pale stool colors. The percentages of recognition were less than about 50% for these stool colors. Conclusion: This study showed that recognition and awareness of prolonged jaundice are low, and acholic stool is not well known. This may lead to delay in diagnosis. Considering the international success of stool color cards, using stool color cards will improve the outcomes of biliary atresia in our country as well. [ABSTRACT FROM AUTHOR]

Purpose: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). Methods: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. Results: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. Conclusions: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications. [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]

Purpose: The presence of alcoholic stool in biliary atresia (BA) patients is the basis of a stool color card (SCC), a screening tool that has led to more patients receiving Kasai portoenterostomy earlier. This study aimed to evaluate the color image processing of stool images captured using smartphones. We propose that measuring digital color parameters is a more objective method for identifying BA stools and may improve the sensitivity of BA screening. Methods: A prospective study was conducted in five hospitals in Thailand between October 1, 2020, and December 31, 2021. Stools from infants presenting with jaundice, acholic stool, or dark-colored urine were photographed. Digital image color analysis was performed, and software was developed based on the color on the original SCC. Sensitivity and specificity for predicting BA stools were compared between the SCC and the software. Results: Of 33 infants eligible for data collection, 19 were diagnosed with BA. Saturation and blue were two potential digital color parameters used to differentiate BA stools. The receiver operating characteristic curve was used to determine the optimum cutoff point of both values, and when saturation =56 or blue =61 was set as a threshold for detecting BA stool, high accuracy was achieved at 81.8% and 78.8%, respectively. Conclusion: Digital image processing is a promising technology. With appropriate cutoff values of saturation in hue, saturation, value and blue in red, green, blue color models, BA stools can be identified, and equivocal-colored stools of non-BA patients can be differentiated with acceptable accuracy in infants presenting with jaundice. [ABSTRACT FROM AUTHOR]

Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury. [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]

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]

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]

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested these 24 mutations affect 24 different genes. We applied unsupervised clustering algorithms to unbiasedly classify the recovered mutants into three classes. Further computational analysis revealed that each of the recovered mutations in these three classes has a unique phenotype on node-subtype composition and distribution within the intrahepatic biliary network. In addition, we found most of the recovered mutations are viable. In those mutant fish, which are already good animal models to study chronic cholestatic liver diseases, the biliary network phenotypes persist into adulthood. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases. [Display omitted] • 24 zebrafish mutants with intrahepatic biliary network defects were identified. • Unsupervised classification algorithms sorted the mutants into subgroups. • Computational analysis revealed the detailed network structures in the mutants. • This work provides computational and biological toolsets for biliary system biology. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is an obliterative cholangiopathy of infancy that results in cholestasis and liver fibrosis. This fibrosis is due to an imbalance in extracellular matrix (ECM) breakdown and deposition. The mechanism by which the progressive injury occurs is not fully elucidated. Matrix metalloproteinases (MMPs) are involved in ECM turnover but also have non-ECM-related functions. Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing BA. Objective: The aim of this study was to assess the hepatic expression of MMP-7 in infants with BA. Patients and methods: The study was a retrospective-prospective case–control study that included 50 patients who were categorized into two groups, BA group (25 patients) and non-BA cholestatic patients as a control group (25 patients). Liver biochemistry, liver biopsy, histopathology, and immunohistochemical staining for primary antibody MMP-7 were performed for all studied patients. Results: Bile duct MMP7 expression was significantly higher in infants with BA than in non-BA cholestasis (P = 0.003), While the hepatic MMP-7 intensity did not differ significantly between both groups (P > 0.05). Bile duct expression of MMP-7 had a significant positive correlation with the BA Score (P = 0.017), while hepatic MMP-7 intensity had a significant positive correlation with alanine transaminase levels (P = 0.007) and a significant negative correlation with γ glutamyl transferase in the BA group (P = 0. 038). There was no statistically significant difference among different stages of fibrosis as regards the median of the hepatic MMP-7 intensity score and MMP-7 bile duct expression in infants with BA. There was no statistically significant difference between infants with successful and failed Kasai as regard the hepatic MMP-7 intensity and its bile duct expression. Conclusion: Bile duct expression of MMP-7 measured by immunohistochemistry is useful for the diagnosis of BA, but it is limited in predicting the stage of liver fibrosis and the outcome of Kasai portoenterostomy (KPE). [ABSTRACT FROM AUTHOR]

Background and aims: Anesthesiologists prefer ketamine for certain surgeries due to its effectiveness as a non-competitive inhibitor of the N-methyl-D-aspartate receptor in the brain. Recently, this agent has also shown promise as an antidepressant. However, ketamine can cause hallucinogenic effects and is sometimes abused as an illicit drug. Ketamine abuse has been associated with liver and bile duct complications. This systematic study aims to better understand cholangiopathy in ketamine abusers by reviewing case reports. Methods and material: In this systematic review, a comprehensive literature search was conducted with the terms "biliary tract diseases" and "ketamine". Case reports and case series of adult patients with documented ketamine abuse and reported cholangiopathy or biliary tract disease were included. We extracted the data of relevant information and the results were reported through narrative synthesis and descriptive statistics. Results: A total of 48 studies were initially identified, and 11 studies were finally included in the review. The mean age of the patients was 25.88 years. Of the 17 patients, 64.7% were men. Symptoms often included abdominal pain, nausea, and vomiting. Most patients were discharged with improved symptoms and liver function. Common bile duct dilation and other findings were observed in imaging results and other diagnostic studies. Conclusion: This review highlights the diverse presentations and diagnostic modalities used in ketamine-induced cholangiography. These patients tend to be young men with deranged liver function tests and abdominal pain, which should be taken into consideration. These patients often require a multidisciplinary approach in their management. [ABSTRACT FROM AUTHOR]

Primary healthcare providers frequently fail to recognize biliary atresia because it closely mimics physiological jaundice. Early detection plays an important role in ensuring the optimal treatment of biliary atresia. Delays in referring to biliary atresia cases remain a problem around the world. The objective of this study was to analyze the knowledge of primary healthcare providers regarding prolonged jaundice as an early sign of biliary atresia. A cross-sectional study was conducted at primary health facilities using a self-administered questionnaire. The data were analyzed using the descriptive method with the assistance of IBM SPSS Statistics for Windows, version 21.0 (IBM Corp., Armonk, N.Y., USA). A total of 271 respondents participated in this study, including midwives (63.8%), nurses (24.4%), and medical doctors (8.5%). It was found that 73.8% of the respondents agreed that infants with prolonged jaundice need to undergo a serum bilirubin level assessment. However, 40.2% of the respondents believed that pale stools and dark urine in yellow infants were symptoms of physiological jaundice. Concerning the definition of prolonged jaundice, 209 (77.1%) respondents provided a response indicating a duration of more than two weeks. A total of 137 (50.6%) respondents stated that biliary atresia is a disease that must be ruled out first in cases of prolonged jaundice. Nevertheless, 86 (31.7%) and 87 (32.1%) respondents also mentioned that breastfeeding jaundice and breast milk jaundice must be considered as potential causes that need to be ruled out, respectively. These results indicated that primary healthcare providers still had limited knowledge regarding cholestasis. Education on prolonged jaundice in primary health facilities requires improvement to enhance the early detection of biliary atresia. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the feasibility of using preoperative imaging indices to predict 2-year native liver survival after the Kasai procedure in patients with biliary atresia (BA). Materials and methods: The retrospective review included 190 BA patients who underwent the Kasai procedure between 2000 and 2020, with preoperative US and/or MRI, excluding cases with less than 2-year follow-up period. Multivariable logistic regression analysis was performed to identify imaging indices to predict 2-year native liver survival. Kasai failure was defined as the need for liver transplantation or death within 2 years of the Kasai procedure. Results: Of the 90 patients included, all had preoperative US, and 61 also had MRI. Kasai failure occurred in 52% (47/90). Preoperative US identified gallbladder length (OR 0.40, 95% CI 0.17–0.95, p = 0.039; cutoff 1.6 cm, AUC 67.66) and biliary cysts (OR 24.64, 95% CI 1.97–308.08, p = 0.013) as significant Kasai failure predictors, with a combined accuracy of 73% (60/82). For patients having both preoperative US and MRI, significant predictors were hepatic artery diameter (OR 6.75, 95% CI 1.31–34.88, p = 0.023; cutoff 2 mm, AUC 73.83) and biliary cysts (OR 23.89, 95% CI 1.43–398.82, p = 0.027) on US, and gallbladder length (OR 0.25, 95% CI 0.08–0.76, p = 0.014; cutoff 1.2 cm, AUC 74.72) and spleen size (OR 2.53, 95% CI 1.02–6.29, p = 0.045; cutoff 6.9 cm, AUC 73.72) on MRI, with a combined accuracy of 85% (52/61). Conclusion: Preoperative US and/or MRI enhance the 2-year native liver survival prediction in BA patients after the Kasai procedure. Clinical relevance statement: BA patients with hepatic artery diameter > 2 mm (US), gallbladder length < 1.6 cm (US) or < 1.2 cm (MRI), spleen size > 6.9 cm (MRI), and absence of biliary cysts (US/MRI) have a decreased likelihood of 2-year native liver survival. Key Points: • Preoperative US and/or MRI can predict the probability of achieving 2-year native liver survival following the Kasai procedure. • Combining US and MRI improved the accuracy to 85% for predicting 2-year native liver survival in BA patients. • The hepatic artery diameter > 2 mm (US), gallbladder length < 1.6 cm (US) or < 1.2 cm (MRI), spleen size > 6.9 cm (MRI), and no biliary cysts (US/MRI) are significant predictors of Kasai failure in patients with biliary atresia. [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]

Ductular reaction and fibrosis are hallmarks of many liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, alcoholic liver disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction- associated steatohepatitis. Liver fibrosis is the accumulation of extracellular matrix often caused by excess collagen deposition by myofibroblasts. Ductular reaction is the proliferation of bile ducts (which are composed of cholangiocytes) during liver injury. Many other cells including hepatic stellate cells, hepatocytes, hepatic progenitor cells, mesenchymal stem cells, and immune cells contribute to ductular reaction and fibrosis by either directly or indirectly interacting with myofibroblasts and cholangiocytes. This review summarizes the recent findings in cellular links between ductular reaction and fibrosis in numerous liver diseases. [ABSTRACT FROM AUTHOR]

Background: We utilized the data from the Saudi national biliary atresia (BA) study (2000–2018) to describe the clinical, biochemical, imaging, and histopathological features of BA and the perioperative clinical practices among local pediatric gastroenterologists. Methods: This is a retrospective, multicenter, nationwide study that included 10 tertiary care governmental hospitals including the four liver transplant (LT) centers in different regions across Saudi Arabia. Results: BA was diagnosed in 204 infants (106 females; 10% preterm). The median age at referral was 65 days. Congenital anomalies were present in 68 patients (33%); 22 were splenic malformation (10.8%). The medians of laboratory investigations were total bilirubin (189 μmol/l), direct bilirubin (139 μmol/l), ALT (164 u/l), and GGT (472 u/l). The level of serum GGT was normal in 26 cases (12.7%). The ultrasound findings included hypoplastic or atrophic gall bladder (GB) (65%), normal GB (30%), and cord sign (5%). A HIDA scan was performed in 99 cases (48.52%). Magnetic resonance cholangiopancreatography (MRCP) was performed in 27 cases (13%). A total of 179 liver biopsies (88%) were obtained. The most common histopathologic findings were bile duct proliferation (92%), canalicular cholestasis (96%), bile plugs (84%), and portal fibrosis (95%). Cholangiography was performed in 139 cases (68%): operative in 122 (60%) and percutaneous in 17 (8%). A total of 143 children (70%) underwent Kasai portoenterostomy (KPE) at a median age of 70 days. After KPE, steroid was used in 37% of the cases and 100 cases (70%) were prescribed prophylactic antibiotics for variable duration (ranging between 3 and 12 months). Conclusion: Our data show marked variation in the diagnostic evaluation and perioperative management of BA cases among the different tertiary centers. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize pre- and postoperative clinical practices. Additionally, normal serum GGT level, normal GB size on ultrasound, and being a premature baby should not preclude the diagnostic workup for BA. [ABSTRACT FROM AUTHOR]

Choledochal cysts (CC) are congenital biliary tract dilatations. Infantile CC (IFCC) in very low birth weight (VLBW) infants is rare. This is a case of a huge IFCC presented in VLBW preterm infant managed with external biliary drainage prior to definitive treatment. Electrolyte imbalance, poor weight gain, and infections were managed during external biliary drainage maintenance. Choledochal cyst excision and Roux-en-Y hepaticoenterostomy were successfully performed when the infant weighed 4.9 kg 5 months later. Delayed definitive treatment with external biliary drainage could be a feasible alternative for managing CC in low-birth-weight infants. [ABSTRACT FROM AUTHOR]

Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histologic findings in patients after LDLT for biliary atresia. Patients aged <19 years who underwent LDLT for biliary atresia at our institution and followed up for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathologic findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathologic fibrosis scores and PV stenosis findings. The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 cut-off index (COI) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (P =. 016) and F1 (P =. 012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n = 5) and 0.72 COI in patients without PV complications (n = 51) (P =. 0001). M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation. [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]

Background: We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants. Methods: In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed. Results: The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1 ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1 ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio. Conclusion: The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants. [ABSTRACT FROM AUTHOR]

The article discusses heterotaxy as a "multi-organ system failure" from an anatomic perspective, commonly presenting to cardiologists and neonatologists due to oxygen delivery abnormalities. Topics include nervous system dysfunction, cardiac complexity in left and right atrial isomerism, pulmonary hypertension, gastrointestinal complications like biliary atresia, and genitourinary issues such as cryptorchidism and infertility in men.

Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods. [ABSTRACT FROM AUTHOR]

Background: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. Methods: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). Results: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. Conclusions: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings. [ABSTRACT FROM AUTHOR]

Purpose: Many patients with biliary atresia (BA) after the Kasai procedure (KP) progress to death or require liver transplantation to achieve long-term survival; however, most cases of death/liver transplantation (D/LT) occur in the early period after KP (usually within 1 year). This study was designed to construct a convenient nomogram for predicting early D/LT in patients with BA after KP. Methods: A BA cohort was established in May 2017, and up to May 2023, 112 patients with 1–5 years of follow-up were enrolled in the study and randomly (ratio, 3:1) divided into a training cohort for constructing a nomogram (n = 84) and a validation cohort (n = 28) for externally validating the discrimination and calibration. The training cohort was divided into two groups: the early D/LT group (patients who died or had undergone LT within 1 year after KP [n = 35]) and the control group (patients who survived through the native liver more than 1 year after KP [n = 49]). Multivariate logistic regression and stepwise regression were applied to detect variables with the best predictive ability for the construction of the nomogram. The discrimination and calibration of the nomogram were internally and externally validated. Results: The Kaplan–Meier (K-M) curve showed an actual 1-year native liver transplantation (NLS) rate of 57.1% and an estimated 2-year NLS rate of 55.2%. By multivariate regression and stepwise regression, age at KP, jaundice clearance (JC) speed 1 month after KP, early-onset PC (initial time < 36.5 days) after KP, sex, aspartate aminotransferase-to-platelet ratio index (APRI), and weight at KP were identified as the independent variables with the best ability to predict early D/LT and were used to construct a nomogram. The developed nomogram based on these independent variables showed relatively good discrimination and calibration according to internal and external validation. Conclusion: Most D/LTs were early D/LTs that occurred within 1 year after KP. The established nomogram based on predictors, including sex, weight at the KP, the APRI, age at the KP, JC speed 1 month after the KP, and early PC, may be useful for predicting early D/LT and may be helpful for counseling BA patients about patient prognosis after KP. This study was retrospectively registered at ClinicalTrials.gov (NCT05909033) in June 2023. [ABSTRACT FROM AUTHOR]

Purpose: Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT). Methods: This study retrospectively reviewed the medical records of pediatric patients aged 0-19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center. The analysis included cases of shunt placement with or without LT. Results: A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement. Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases. A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported. Conclusion: Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT. [ABSTRACT FROM AUTHOR]

Celiac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. Contrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. 305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). MAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population. [Display omitted] [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]

Aim: The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance cholangiopancreatography (MRCP). Materials and Methods: It is a prospective observational study in a cohort of patients who have survived with a complete jaundice-free period for at least 1 year. MRCP was done to look for various intrahepatic architectural changes during their last visit. Findings were correlated with liver functions and growth and development. Results: Twenty-one patients were included in the study. The male-to-female sex ratio was 1.6:1, the median age at surgery was 75 days (18-140 days), and the median age at magnetic resonance imaging (MRI) was 4 years (18 months-18 years). More than 2 years of follow up was in seven patients. Left lobe hypertrophy was observed in six patients, right lobe hypertrophy was in three patients, intrahepatic biliary tract dilatation was in five patients, and altered signal intensity between intrahepatic ducts was seen in five patients. In addition, hypointense foci in the spleen were seen in one patient. Twelve children had normal weight for their age, ten children had the normal height for their age, and gamma-glutamyl transferase was elevated in all children. Only four children had a history of fever and jaundice. Conclusions: The patients who survive after successful surgical intervention have near-normal liver gross architecture as on MRI/MRCP. Occasional findings of dilatation and lobar atrophy/hypertrophy are possible, especially in those with a history of cholangitis. The survivors also have acceptable growth parameters and normal liver functions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally. In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements. We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old. Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality. Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era. [ABSTRACT FROM AUTHOR]

For patients with Biliary atresia, antibiotic prophylaxis after Kasai portoenterostomy is a common practice. Societal guidelines often cite one reference as supportive evidence for this practice. In this paper, we go back to review the quality of this evidence and suggest more research is required to demonstrate the efficacy of antibiotic prophylaxis in this population. [ABSTRACT FROM AUTHOR]

Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P =.0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. Pre-transplant TPN was safe and effective for patients with end-stage BA. [ABSTRACT FROM AUTHOR]

Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT, but the adequate dose after pediatric LDLT was unknown. Here, we report micafungin blood concentrations after pediatric LDLT and discuss its safety and adequate dosing. Pediatric patients with data on micafungin concentrations after LDLT were identified. Those with surgical complications were excluded. All patients received standard tacrolimus-based immunosuppression. A micafungin dose of 1 mg/kg was administered once daily for 10 days starting on postoperative day (POD) 1. The trough and peak micafungin blood concentrations were evaluated on PODs 1, 4, 7, and 10. Beta D glucan levels and liver function tests were assessed to determine micafungin effectiveness and safety. Ten patients were enrolled, with a median age of 1.2 years. The median graft vs body weight ratio was 2.7%. The primary diseases were biliary atresia (n = 7), Alagille syndrome (n = 2), and progressive familial intrahepatic cholestasis type 2 (n = 1). Mean peak micafungin levels were 4.47, 6.27, 5.47, and 5.47 µg/mL on PODs 1, 4, 7, and 10, respectively. Mean trough levels were 2.03, 1.88, and 2.66 µg/mL on PODs 4, 7, and 10, respectively. The micafungin half-lives were 13.7, 14.7, and 14.0 hours on PODs 4, 7, and 10, respectively. Beta D glucan levels were 4.4 pg/mL and 3.7 pg/mL before and after transplantation, respectively, indicating no significant difference (P =.3). No clinical fungal infections were observed. Micafungin administration is safe and effective after pediatric LDLT. [ABSTRACT FROM AUTHOR]

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

Purpose: Patients with biliary atresia (BA) and cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy (KPE) than uninfected patients, suggesting a rationale for antiviral treatment (AVT). We aimed to describe the incidence of CMV infection and of AVT in BA patients, and to detect any differences between infected and uninfected patients to conclude if AVT is of use. Methods: Data on BA patients who underwent KPE 2004–2020 were retrospectively collected, and the outcome was analyzed with regard to CMV status. Results: Fifteen out of forty-six (33%) BA patients had signs of ongoing CMV infection. They did not differ significantly from the CMV-negative patients regarding rate of prematurity, birth weight, or biochemical markers but were slightly older at KPE. All patients received steroids postoperatively and all patients with ongoing CMV infection received AVT with very good effect on viremia and without major side effects. The AVT consisted of oral valganciclovir (10–40 (– 58) mg/kg/d) or intravenous ganciclovir (5.3–11 mg/kg/d). Conclusion: Ongoing CMV infection is common in this group of patients. The viremia can effectively be treated with AVT without any major side effects. Larger, randomized studies are needed to clarify the possible effect on clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: The role of the laparoscopic approach for the Kasai procedure in the management of biliary atresia is still controversial. The aim of this study is to compare the long-term results of the laparoscopic Kasai procedure (LKP) to the open Kasai procedure (OKP). Methods: A randomized clinical trial was carried out from October 2009 to March 2017. Patients diagnosed with biliary atresia type III were randomized into 2 groups: one group underwent LKP and the other group–OKP. All the surgical procedures were performed by the same surgeon with the same technical principles. The long-term outcomes were compared between the two groups. Results: 61 patients underwent LKP and 61 patients–OKP, with a median age at the surgery of 79.7 days. The two groups had no significant differences regarding the patients’ baseline characteristics. At follow-up up to 142 months, the jaundice-free rate at the 6th postoperative month for LKP and OKP was 52.5% and 60.7%, respectively (p = 0.23). The 10-year cumulative survival after LKP tended to be inferior to OKP, respectively 44.3% vs. 58.9% (p = 0.09). Conclusions: In this study, the long-term results of LKP tended to be inferior compared to OKP although the differences were not significant. [ABSTRACT FROM AUTHOR]

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