Ileal bile acid transporter inhibitors (IBATi) are a new, attractive therapeutic mechanism to alter the enterohepatic circulation through depletion of the bile acid pool by blocking bile acid reuptake in the ileum leading to improvements in pruritus and liver function in cholestatic liver diseases. These drugs may also have an impact on immunity, the gut microbiome, and motility. IBATi are approved in Japan for the treatment of idiopathic chronic constipation. There are two IBATi, maralixibat and odevixibat, that have been extensively investigated in clinical trials and are FDA approved for cholestatic pruritus in progressive familial intrahepatic cholestasis and Alagille syndrome. Clinical trials exploring IBATi in other cholestatic conditions, such as biliary atresia, primary biliary cholangitis, and primary sclerosing cholangitis, are currently ongoing. In this review, we will outline the emerging data regarding the physiology and mechanism of action for the IBATi class, an overview of clinical trials that led to the approval of maralixibat and odevixibat, ongoing clinical trials in adult cholestatic liver diseases, and the future of this drug class in systemic apical sodium bile acid transporter inhibitors.

Geography and diagnostic testing practices impact the timing of Kasai portoenterostomy for biliary atresia.

Human cytomegalovirus (HCMV) is associated with bile duct disorders in immunocompetent and immunocompromised individuals, including sclerosing cholangitis, biliary structures, AIDS cholangiopathy, biliary atresia (BA), and post-transplant biliary complications. Despite these clinical associations, it remains unknown whether HCMV can directly infect the bile duct epithelium and cause pathogenesis. Here, we establish a human iPSC-derived cholangiocyte-like cell (CLC) organoid model that can be infected by HCMV, which results in reduced organoid growth, a deformed structure, and a loss of barrier function. Bulk RNA sequencing (RNA-seq) showed that the HCMV-infected organoids had highly enriched expression of genes involved in the epithelial-mesenchymal transition (EMT) pathway. Importantly, blockade of TGF-β signalling abrogates the EMT induction effect in the HCMV-infected CLC organoids. Furthermore, single-cell RNA-seq indicates that HCMV infection occurred in different clusters with distinct viral and host gene expression profiles and the analysis shows increased expression of EMT and TGF-β signalling-related genes. The findings are confirmed in BA patient liver tissues by examining HCMV-DNA+ cells. Two modes of infection by HCMV are found in these CLC organoids, which show productive and latency-like features. This study shows that HCMV infection induces EMT in cholangiocytes that may contribute to the cholangiopathy seen in various diseases.

Biliary atresia (BA) is an obstructive cholangiopathy of the newborn. Early diagnosis improves outcomes, but due to rarity and nonspecific presentation, referral is often delayed. Incorporation of BA into newborn screening (NBS) using dried blood spots (DBS) is desirable. Matrix metalloproteinase 7 (MMP-7) is a highly specific and sensitive marker for BA in serum and DBS and has been proposed as an appropriate screening parameter. We aimed to evaluate MMP-7 levels in DBS from patients with BA to assess its potential for NBS. Original DBS NBS cards of infants with BA (n=49) were retrospectively obtained from screening laboratories. Additional DBS and blood samples were collected at Kasai portoenterostomy (n=5). To assess MMP-7 stability, a fresh DBS sample was stored at different intervals before freezing. Healthy newborns served as controls (n=24). MMP-7 was measured by ELISA and correlated with BA type, outcome, fibrosis score, and bilirubin levels. Diagnostic performance was assessed by ROC analysis in both the study cohort and a modeled real-world prevalence setting. Patients with BA showed significantly higher MMP-7 levels than controls (BA 22.80ng/mL±12.28, HC 13.82ng/mL±2.97, p<0.001). Exploratory stability assessment suggested a time-dependent decrease in MMP-7 concentrations during room temperature storage, which appeared moderate within the initial days. MMP-7 levels at birth did not correlate with clinical parameters at Kasai portoenterostomy. ROC analysis demonstrated good test performance within our study cohort; however, extrapolation to real-world prevalence yielded insufficient screening performance. MMP-7 is elevated in BA patients' DBS at birth, but current performance characteristics are insufficient for reliable NBS. Larger studies and multiparametric approaches may be needed to improve screening feasibility.

Background In pediatric biliary cirrhosis secondary to biliary atresia (BA), hepatic lobules are disrupted to form pseudolobules. How the hepatic circulation is reorganized remains a poorly characterized issue. Purpose To reproduce the three-dimensional (3D) structural and remodeling alterations of BA-induced pseudolobules via phase-contrast CT (PCCT) and reveal their circulatory self-rescue mechanism. Materials and Methods In this retrospective study, residual donor normal liver tissue samples and BA-affected liver samples collected between November 2013 and April 2024 were imaged with PCCT. Combined with 3D visualization technology, the spatial anatomic morphologic characteristics of the veins, arteries, and sinusoidal system within the hepatic lobules were reproduced based on liver histopathologic examination. Key indexes such as the number of inlet and outlet venules, sinusoidal volume fraction, and anisotropy, were determined to characterize the structural remodeling of the circulatory pathway, from portal and arterial inflow through the sinusoidal exchange network to hepatic venous outflow, in patients with BA. All indicators were analyzed with generalized estimating equations, and the multiple test correction was performed by conducting Holm-Bonferroni correction, with P < .05 indicating statistical significance. Results Normal livers from three donors (median age, 36 months; IQR, 12-132 months; two male donors) and 25 patients with BA (median age, 7.00 months; IQR, 5.8-10 months; 17 male patients) were analyzed. The mean number of inlet venules decreased from 253.07 ± 70.99 (SD) in normal lobules to 138.80 ± 28.12 in pseudolobules (P < .001). The mean number of inlet arterioles increased from 3.93 ± 1.39 in normal lobules to 5.65 ± 2.43 in pseudolobules (P < .001). The number of outlet venules in pseudolobules decreased by 35% compared with that in normal lobules (mean, 105.02 ± 42.47 vs 161.96 ± 42.47; P < .001). In the sinusoidal system, the volume fraction in pseudolobules increased by 51% compared with that in normal lobules (mean, 40.42 ± 6.28 vs 26.72 ± 6.32; P < .001), especially in the inlet area, where this value nearly doubled (mean, 44.47 ± 4.73 vs 23.44 ± 5.95; P < .001). Mean anisotropy decreased from 0.53 ± 0.02 in normal lobules to 0.51 ± 0.03 in pseudolobules (P < .001). Conclusion The lobular circulation remodeling mechanism in BA-induced pseudolobules, from the inlet channel to the exchange network and outlet channel, was comprehensively revealed via PCCT. © RSNA, 2026 Supplemental material is available for this article.

SSL-OHE: A self-supervised ensemble approach for early diagnosis of biliary atresia from sonographic images

Cystic biliary atresia (CBA) is a rare variant of type III biliary atresia (BA). This study aimed to investigate the clinical features and prognosis of CBA in comparison to non-CBA cases. A retrospective analysis was conducted on 196 children diagnosed with type III BA between December 2016 and December 2020. This cohort included 22 cases in the CBA group and 174 cases in the non-CBA group. All children underwent Kasai portoenterostomy (KPE) and were subjected to standardized follow-up with a maximum of 5years. We compared and analyzed the age at surgery, postoperative jaundice resolution rates, native liver survival rates, and complication rates between the two groups. Patients in the CBA group underwent surgery at a significantly younger age compared to those in the non-CBA group (P < 0.001). There were no statistically significant differences in preoperative liver function indices, such as ALT and AST, between the two groups (P > 0.05). Postoperative cholangitis occurred less frequently in the CBA group than in the non-CBA group (P = 0.009). The rates of jaundice resolution at 6 and 12months post-surgery were significantly higher in the CBA group than in the non-CBA group (P < 0.05). The five-year native liver survival rate was 67.87% for the CBA group, compared to 40.10% for the non-CBA group (P < 0.0233). The overall prognosis for CBA is superior to that of non-CBA. Children with CBA received surgical intervention earlier; the postoperative jaundice resolution rate and five-year native liver survival rate of the children were higher than that of non-CBA. These findings provide valuable clinical guidance for the individualized treatment and follow-up management strategies for CBA.

To evaluate the diagnostic yield of prenatal imaging for fetal liver lesions and to characterize associated postnatal outcomes. We conducted a single-center retrospective review of prenatally diagnosed liver lesions between 2013 and 2023. Data collected included prenatal imaging findings, postnatal diagnoses, neonatal outcomes, and management strategies. Thirty women were referred at a median gestational age of 31.1 weeks [IQR: 27.5-33.4]. Lesions were classified as cystic (53%), solid (20%), mixed (17%), or vascular (10%). Postnatal diagnoses included hemangioma (33%), hepatic cyst (27%), choledochal cyst (10%), arteriovenous malformation or portosystemic shunt (13%), mesenchymal hamartoma (7%), biliary atresia (3%), focal nodular hyperplasia (3%), and unknown (6%). Overall diagnostic concordance between prenatal and postnatal findings was 69%. Fetal complications occurred in 40% of cases, most commonly cardiac overload (n=8), intrauterine growth restriction (n=3), and mass effect (n=2). Hypervascularized lesions were significantly associated with fetal compromise (p<0.001). No cases of intrauterine fetal demise were observed. Fetal MRI was performed in 70% of cases and improved diagnostic accuracy in two cases. Median gestational age at delivery was 38.0 weeks [IQR: 36.6-39.1]. Postnatal management included expectant observation (67%), surgery (20%), beta-blockers (7%), and embolization (3%). After a median follow-up of 32.5 months [IQR: 14.8-60.9], 38% of lesions had regressed spontaneously. One infant died from complications following embolization. Most fetal liver lesions are associated with favorable outcomes. However, hypervascularized lesions are predictive of in utero complications and warrant close monitoring. Fetal MRI may improve diagnostic accuracy and guide post-natal management.

Biliary atresia (BA) is a serious condition and the leading cause for liver transplantation in children. The exact cause for BA is currently unknown, with one suggested mechanism being a viral infection. Cytomegalovirus (CMV) is the most common viral infection in BA patients and was previously known to be associated with worse outcomes, including liver fibrosis. Our study aimed at investigating the association between CMV infection and liver fibrosis in BA patients who underwent the Kasai procedure at our institution. This study was a retrospective analysis of medical records from BA patients who underwent the Kasai procedure between January 2019 and July 2024 at our hospital. Our study involved 15 male and 23 female BA patients. The proportion of CMV-infected patients (n = 11) was lower than that of the non-CMV-infected BA patients (n = 27). The association between CMV infection status and liver cirrhosis (p = 1.0) was statistically insignificant. However, the age at the Kasai procedure showed a statistically significant association with cirrhosis (p = 0.027; odds ratio [OR] = 7.20; 95% confidence interval [CI] = 1.27-40.7). Moreover, a multi-variate analysis revealed a strong association between the age at the Kasai procedure and liver cirrhosis (p = 0.029; OR = 7.37; 95% CI = 1.22-44.42). Our study's findings suggest that CMV infection might not significantly affect the degree of liver fibrosis in BA patients following the Kasai procedure. Furthermore, the age at which the Kasai procedure is performed might influence the development of liver cirrhosis in these patients. These insights could reshape our understanding of BA and guide future research and clinical practice.

Neonatal Cholestasis in India: The Urgent Case of Biliary Atresia

This report describes endovascular treatment of saccular portal and splenic vein pseudoaneurysms using n-butyl-2-cyanoacrylate (nBCA) with balloon assistance. The first case was a 39-year-old female who developed a gastric ulcer after undergoing living-donor liver transplantation (LDLT) due to liver failure following surgery for congenital biliary atresia. Two saccular pseudoaneurysms were developed in the main trunk of the splenic vein, caused by the gastric ulcer, and protruded into the stomach. The second case was a 43-year-old male who presented with a saccular pseudoaneurysm in the main portal vein after LDLT. Because these pseudoaneurysms caused severe hemorrhage in both cases, endovascular treatments were performed via the transhepatic approach in the first case and via the ileocolic approach in the second case. Each pseudoaneurysm was successfully packed with 50% nBCA under balloon-assisted flow control, while preserving the parent veins. Balloon-assisted nBCA filling of saccular portal venous system pseudoaneurysms is an effective endovascular treatment that can preserve blood flow in parent veins. This technique could become a treatment option, especially when surgery or stent graft placement is difficult for clinical or technical reasons or due to limited stent availability.Clinical ImpactThis report presents an alternative endovascular method for embolizing portal venous system pseudoaneurysms while preserving parent veins. This approach, consisting of nBCA filling with balloon-assisted flow control, offers an alternative to stent graft or covered stent placement. Balloon-assisted nBCA filling can become a viable treatment option for saccular portal venous system pseudoaneurysms, particularly when surgery or stent graft placement is difficult for clinical or technical reasons, or due to limited stent availability.

Cholestatic liver injury, characterized by direct exposure of hepatocytes to retained bile components with elevated concentrations, represents a common manifestation of various hepatobiliary disorders with persistent threats to long-term patient survival despite existing therapies. As the primary route for copper elimination, cholestasis raises questions about the role of copper in cholestatic liver injury and its specific molecular mechanisms. Our single-center retrospective study revealed elevated serum copper levels in subjects with increased gamma-glutamyl transferase compared to controls. Single-cell sequencing of biliary atresia (BA) patients’ cholestatic liver specimens demonstrated downregulation of FDX1, a key cuproptosis marker, in BA hepatocytes. Bile duct-ligated rats under high-copper diets exhibited accelerated liver injury, attenuated by copper chelator tetrathiomolybdate (TTM). In vitro, copper chloride/elesclomol-induced DLAT monomer reduction and oligomerization alongside impaired lipoylation. Given the special coexistence of copper overload and accumulated bile components within the hepatic microenvironment, notably, we found that taurocholic acid potentiated hepatic copper accumulation under cholestatic conditions. Mechanistically, transcriptomic analysis implicated smoothened signaling inhibition in cuproptosis progression, with smoothened agonist (SAG) restoring DLAT expression and cellular viability. Interestingly, FDX1 overexpression enhanced cuproptosis resistance of hepatocytes through DLAT monomer stabilization and LIAS-mediated lipoylation. Cholestasis-induced copper overload drives liver injury via taurocholic acid-exacerbated and FDX1-mediated cuproptosis. Our findings propose TTM and SAG as therapeutic candidates and reveal complex FDX1 regulatory roles, suggesting novel approach for managing cholestatic liver injury.

Status, Advances, and Challenges in Pediatric Liver Transplantation in Africa: A Scoping Review.

Background: Liver transplantation has transformed medicine, especially for patients with advanced liver disease and hepatocellular carcinoma, improving their lifespan and quality of life. Objective: To assess the one-year survival rate post-liver transplantation and analyze the factors influencing survival. Methods: A retrospective study conducted at Baghdad Gastroenterology Hospital analyzed data from liver transplant referrals over the last 5 years, based on the Model for End-Stage Liver Disease score. 100 patients were classified as children (≤18 years) and adults (≥19 years) and followed up for one year post-transplant. Mortality analysis considered various etiological, clinical, and sociodemographic factors. Results: In adults, males were predominant among both patients (66%) and donors (71.7%). The most frequent cause was cryptogenic cirrhosis (39.62%), then viral and autoimmune hepatitis (20.75% and 18.87%), respectively. Of the 53 adult patients, 5 died (9.43%), and 48 survived (90.57%). The age gap and BMI were significantly different. In pediatrics, biliary atresia was the most common cause (36.17%). Of the 47 pediatric patients, 16 died (34%) and 31 survived (66%). However, there were notable differences in the causes of liver cirrhosis between deceased and surviving patients. BMI and age gap between donors and recipients significantly affect survival in adults, while biliary atresia, Caroli disease, and hyperoxaluria have the highest one-year mortality in pediatric patients. Conclusions: Over 90% of adults and 66% of children survive a year after receiving a liver transplant; in adults, age and BMI differences have a major impact. In contrast, pediatric survival was affected by the etiology of cirrhosis.

To assess the short-term outcome of Kasai portoenterostomy (KPE) in infants with biliary atresia (BA) and to identify the prognostic factors for successful KPE. The study included 127 infants with BA who presented to the Pediatric Hepatology Unit, Cairo University over a period of 10 y. All patients were followed up for 6-mo post-KPE. Data retrieved from the patients' files included: history, clinical examination and investigations done at the time of presentation and after 6 mo of KPE. A successful outcome was defined as jaundice clearance after 6 mo of KPE. Age at KPE ranged from 30-180 d. Marked fibrosis was present more frequently among older patients. Eighty-seven patients (67%) had yellow-colored stools immediately after KPE. Jaundice clearance 6 mo after KPE was achieved in 40 patients (31.5%). Lower age at time of KPE was significantly associated with successful KPE (P = 0.03). Steroid therapy post-KPE did not show improvement in jaundice clearance. KPE had a 6-mo short term successful outcome in one-third of patients with BA. Younger age at KPE is an important prognostic factor to increase the rate of jaundice clearance. Steroids therapy failed to achieve a favorable outcome.

Biliary Atresia: A Meta-analysis of Indian Studies.

ABSTRACTIntroductionCholestatic liver disease is the leading indication for pediatric liver transplantation (LT). Early detection and optimal care are often limited by socioeconomic barriers including racial disparities. This study examined racial disparities in demographics, waitlists, and post‐transplant outcomes among pediatric LT recipients with cholestatic liver disease.MethodsAll pediatric patients (≤ 18 years) who were listed or received LT for cholestatic liver disease (Biliary Atresia, Caroli's, Choledochal cyst, PSC, PFIC, Alagille, and other non‐specified cholestatic diseases) between 2010 and 2024 were retrospectively identified using the United Network for Organ Sharing (UNOS) database. The primary outcome of the study was waitlist mortality, graft failure, and post‐transplant mortality stratified by race, specifically non‐Hispanic whites (NHW), non‐Hispanic blacks (NHBs), Hispanics, and others.Results3501 pediatric patients underwent LT for cholestatic liver disease: 1663 (47.5%) were NHW, 795 (22.7%) were Hispanic, 648 (18.5%) were NHB, and 395 (11.3%) were of other races. NHW recipients were more likely to have private insurance (56.7% vs. 18.2%, p < 0.01) and experienced shorter waitlist times than Hispanic patients (175.9 vs. 189.4 days, p < 0.01). The 1‐year survival rate was lower in NHB than in NHW recipients (94.8% vs. 96.8%, p = 0.04), with no significant difference at 5 years (93.7% vs. 95.4%, p = 0.13). Hispanic patients had similar 1‐year (95.9%, p = 0.26) and 5‐year (93.3%, p = 0.06) survival rates to NHW. NHB recipients had a significantly increased risk of mortality with a hazard ratio (HR) of 1.53 [95% CI: 1.05–2.22]. Predictive modeling using extreme gradient boosting showed a relative likelihood of increased mortality in NHB (3.91%) and Hispanic (3.14%) recipients.ConclusionRacial disparities significantly affect post‐transplant outcomes in pediatric cholestatic liver disease. NHB and Hispanic children face a risk of higher mortality despite similar waitlist outcomes, highlighting the need for targeted interventions to promote equity in pediatric liver transplantation.

Alagille Syndrome (ALGS) is a rare multisystem disorder of autosomal dominant type which is primarily caused due to mutations in the JAG1 gene and, less commonly, NOTCH2, both integral to Notch signalling. Clinically, ALGS is further characterised by cholestatic liver disease because of intrahepatic bile duct paucity, along with some cardiac and skeletal abnormalities, ocular defects, renal involvement, and distinct facial features. Diagnosis of ALGS depends upon the presence of at least three of five main clinical features, which are later supported through liver biopsy, genetic testing, and imaging. Differential diagnosis of ALGS includes biliary atresia, Progressive Familial Intrahepatic Cholestasis (PFIC), neonatal hepatitis, and syndromes with overlapping phenotypes such as Noonan and Kabuki syndromes. Management in such cases is largely supportive, which mainly focuses on relieving cholestasis and pruritus, along with proper nutritional adequacy, and addressing systemic complications. Liver transplant is reserved only for end-stage disease or intractable symptoms. A multidisciplinary approach is an essential aspect of treatment to improve patient outcomes, along with quality of life.

Neonatal cholestatic jaundice (cholestasis) has extensive aetiologies and occurs frequently in preterm infants in neonatal intensive care units (NICUs). Current multinational guidelines involve wide-ranging investigations suited to general newborn populations without validation in NICU settings. We retrospectively reviewed New Zealand's guidelines for investigating cholestatic jaundice in the NICU. Infants admitted to one tertiary NICU between 2008 and 2022 with direct bilirubin ≥20 µmol/L and percentage of total bilirubin ≥20% were identified from laboratory records. Investigations, health data and outcome data were obtained from clinical records. Cholestasis was detected in 208 (1.5% admissions) with median gestational age of 27 weeks and birth weight of 942 g. Eight (3.8%) had primary liver diseases, all presenting in the early newborn period. Four (1.9%) with biliary atresia manifested cholestasis and acholic stool within 1-month postnatal age; two were born preterm and survived >5 years transplant-free post-portoenterostomy. There were no delayed or missed diagnoses of primary liver disease. The remaining 200 (96.2%) had hepatobiliary dysfunction related to preterm comorbidities, intestinal failure-associated liver disease, cytomegalovirus infection, rare extrahepatic congenital disease or unknown causes. Investigations included liver biopsy in 28 (13.5%), hepatobiliary scintigraphy in 7 (3.4%), intraoperative cholangiography in 4 (1.9%) and 1 (0.5%) percutaneous cholangiogram. Overall, invasive testing for rare congenital diseases was done infrequently. Most NICU infants with cholestasis did not have congenital diseases, and the small minority who did were all distinguishable by clinical factors regardless of gestation.

BackgroundBiliary atresia (BA) is a rare and severe cholangiopathy. Accurate prediction of outcomes following Kasai portoenterostomy (KPE) is crucial for guiding individualized treatment strategies. This study primarily aimed to investigate the prognostic value of various laboratory biomarkers, including preoperative serum matrix metalloproteinase-7 (MMP-7) level.MethodsThis prospective cohort study included consecutive infants with conjugated hyperbilirubinemia who were evaluated with serum MMP-7, liver two-dimensional shear wave elastography (2D-SWE), and other laboratory tests from July 2020 to September 2024. The reference standard for diagnosis was intraoperative cholangiography. We recorded the follow-up of native liver survival (NLS) time post-KPE longer than 2 years. Area under the curve (AUC) analysis, Kaplan-Meier survival analysis, Cox regression analyses, and establishment of an NLS nomogram were performed.ResultsA total of 154 patients (median age 66 days), including 83 BA infants and 71 non-BA cholestatic infants, were included in the study. Serum MMP-7 distinguished infants with BA from other cholestatic infants, with a high diagnostic AUC of 0.95 [95% confidence interval (CI): 0.91–0.99]. Multivariate Cox regression analysis identified serum MMP-7 [hazard ratio (HR) 3.31], serum γ-glutamyltransferase (GGT) (HR 3.81), age at surgery (HR 2.21), and liver 2D-SWE (HR 11.47) as independent risk factors for NLS. An NLS nomogram based on the serum MMP-7, serum GGT, and age at surgery achieved a concordance index of 0.76 (95% CI: 0.67–0.85). A risk score was also established to stratify high-risk and low-risk patients post-KPE.ConclusionsThe preoperative serum MMP-7 is valuable for predicting post-KPE prognosis. The novel nomogram and risk score effectively predict NLS following KPE, offering critical and practical guidance for optimizing BA treatment strategies.