Search Results (119)

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. Race also significantly impacts disparities in healthcare utilization and clinical outcomes. Our study focused on the impact of race on admission, clinical outcomes, and disposition of cholangiocarcinoma. Methods: We performed a retrospective analysis of cholangiocarcinoma-related hospital admissions, using the National Inpatient Sample for the year 2022. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, and Other. The data analysis was performed using STATA/BE version 18.5. Univariable and multivariable logistic regression models were applied to evaluate the relationship between race and clinical and healthcare utilization outcomes. Results: In 2022, 7479 hospitalizations were recorded for cholangiocarcinoma in the United States. Among these, 65.99% were White, 13.27% Hispanic, and 10.13% African American. There was a statistically significant difference in gender distribution across racial groups (p < 0.001), with males comprising the majority in all groups. Males outnumbered females in all racial groups except among the Hispanic group. Significant racial disparities in mortality were observed, with White patients showing a mortality rate of 6.69%, compared to higher rates among African American (9.76%), Native American (8.51%), and Asian or Pacific Islander (8.09%) patients, while Hispanic (5.04%) and Other (5.88%) groups had lower rates (p < 0.001). Conclusions: The study underscores the racial disparities among cholangiocarcinoma hospitalizations, with African American, Native American, and Asian patients facing disproportionately higher mortality and poorer in-hospital outcomes compared to White patients. This analysis highlights the healthcare strategies and policy reforms to promote equitable treatment by mitigating these disparities and to improve cholangiocarcinoma outcomes. Full article

Background: Cholangiocarcinoma (CCA) of the liver is a highly aggressive cancer that arises from malignant cells in the bile ducts. Radical surgery remains the only curative option, but major liver resection carries high perioperative risks. This study investigates the predictive value of preoperative bone mineral density (BMD), measured via CT, for perioperative complications, mortality, and long-term outcomes. Methods: The analysis included 202 patients who underwent curative-intent surgery for intrahepatic cholangiocarcinoma (iCCA; n = 97) or perihilar cholangiocarcinoma (pCCA; n = 105) between 2010 and 2019. Preoperative bone mineral density (BMD) was assessed using computed tomography segmentation at the level of the 12th thoracic vertebra. Osteopenia was defined according to established cutoffs. Results: Osteopenia was highly prevalent in both iCCA (53/97, 54%) and pCCA (54/105, 51%) subcohorts. Patients suffering from osteopenia were significantly older than those without (71.1 [62–76.6] years vs. 61.3 [52.9–69.2] years; p < 0.001). Alteration in BMD did not demonstrate a significant prognostic effect in terms of perioperative morbidity (Mann–Whitney U; comprehensive complication index—CCI: 34 [9–56] vs. 40 [21–72] p = 0.185; iCCA: p = 0.803; pCCA: p = 0.165). The median overall survival in our cohort was 19 [14–25] months. Patients with osteopenia did not exhibit a significantly different overall survival compared to those with normal bone mineral density (log-rank p = 0.234). Conclusions: In contrast to our previous observations in other oncological patient cohorts, osteopenia alone had no significant negative impact on clinical outcomes in our large European cohort of patients undergoing curative-intent surgery for CCA. To validate these findings, further prospective studies are warranted. Full article

Background/Objectives: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using a fully covered self-expandable metal stent (FCSEMS) is an alternative to endoscopic retrograde cholangiopancreatography for biliary drainage; however, FCSEMSs may cause intrahepatic bile duct (IHD) obstruction and cholangitis. In this study, we developed an FCSEMS with multiple self-made side holes at its tip and evaluated its safety and efficacy. Methods: This retrospective study included 100 patients who underwent EUS-HGS with FCSEMS placement between April 2022 and October 2023. Fifty patients received a conventional FCSEMS, and 50 received an FCSEMS with multiple self-made side holes. Technical and clinical success, residual contrast in the IHD, recurrent biliary obstruction (RBO), and adverse events (AEs) were then evaluated. The clinical success rates were 98% and 90% for the side hole and conventional FCEMS groups, respectively. The amount of residual contrast in the IHD was lower in the side hole group (0% vs. 12%, p = 0.027). RBO incidence was significantly lower in the side hole group (8% vs. 30%, p < 0.001), with migration as the primary cause in the conventional group. Early AEs, including segmental cholangitis, occurred only in the conventional group. During reintervention, all stents were safely removed. Conclusions: The FCSEMSs with multiple side holes reduced IHD occlusion and cholangitis, improving biliary drainage and safety. Further studies are needed to confirm these findings. Full article

Background and Objectives: Hepatolithiasis (HL), or intrahepatic bile duct stone disease, shows regional variation and is a rare condition in Western countries. While cases from East Asia are often linked to chronic biliary infections and brown pigment stones, Western HL more frequently involves cholesterol or black pigment stones, typically in the context of prior cholecystectomy, biliary interventions, or congenital anomalies. The disease is generally associated with significant morbidity, including recurrent cholangitis, biliary strictures, and risk of cholangiocarcinoma. This study aimed to characterize HL disease in an Italian case series. Materials and Methods: We retrospectively reviewed 1450 patients with biliary stone disease treated between 2010 and 2024. HL was diagnosed in 14 patients (0.96%). Clinical records, imaging (ultrasound, CT, magnetic resonance cholangiopancreatography—MRCP, cholangiography), bile cultures, and stone composition (categorized as cholesterol, brown pigment, black pigment, or mixed using FTIR/XRD) were analyzed. Results: Among the 14 patients (mean age: 60.1 years; 64.3% female), 71.4% presented with recurrent cholangitis, while 28.6% were asymptomatic. Stones were left-sided in 57.1%, right-sided in 21.4%, and bilateral in 21.4%. Stone composition was cholesterol/mixed in 50%, brown pigment in 35.7%, and black pigment in 14.3%. Risk factors for bile stasis were present in 71.4% of cases. Bile cultures (available in nine cases) were positive in 77.8%. MRCP was highly effective for diagnosis. Hepatectomy achieved complete resolution in 35.7% of patients with unilobar disease; endoscopic/percutaneous therapy had a 44.4% recurrence rate. Interestingly, no cholangiocarcinoma was observed over a median follow-up of 4.8 years. Conclusions: Western HL is a rare, heterogeneous disease with distinct features. Cholesterol-predominant, infection-negative cases suggest a metabolic or surgical etiology. Hepatectomy offers durable outcomes in unilobar disease. Advanced imaging (MRCP, cholangioscopy) and personalized strategies are key to effective management. Full article

Objective: To provide an overview of the technique and normal values of ultrasound studies of the bile system based on the published literature. Methods: A literature search for ultrasound studies with measurements of the bile ducts in healthy subjects was performed. Relevant data published between 1975 and end of 2024 were extracted, discussed, and complemented with the own experiences of the authors. The clinical implications are presented and discussed. Results: For the diameter of the common bile duct, reference values between 5 and 9 mm have been published. The main influencing factors are age and history of cholecystectomy, and other factors to be considered are discussed here. The cut-off for the common bile duct wall is set at 1.5 mm. The literature on measurements of intrahepatic bile ducts is scarce. A diameter of <2–3 mm can be considered normal. The method of ultrasound examination is presented here, as well as a comparison with other imaging methods and their clinical implications. Conclusions: Standardized measurement techniques and normal values in the context of influencing factors are crucial for the ultrasound examination of the bile system. Full article

Background/Objectives: Obstruction of the biliary duct may be caused by various conditions ranging from chronic inflammation to neoplasia, including cholangiocarcinoma (CCA). While the definite histological diagnosis of intrahepatic lesions is relatively straightforward, the diagnostic workup of biliary duct stenosis can be challenging, despite the availability of novel tools for intraductal diagnosis. This proof-of-principle study aimed to investigate whether microRNAs (miRNAs) from bile duct stents may be used as biomarkers to differentiate between various bile duct diseases. Methods: For this purpose, we included 100 patients with one or more bile duct stents for various reasons, including malignant disease (n = 40), stenosis due to liver transplantation or surgery (n = 60), and cholangitis (n = 42). During endoscopic retrograde cholangiography, the stents were collected, and miRNA analyses were performed to evaluate miR-16, miR-21, and miR-223. Results: All studied miRNAs were successfully detected from the specimens obtained from the bile duct stents and were comparable in different stents from the same subjects. Following normalization, significant increases in miR-16, -21, and -223 levels were identified in patients with cholangitis compared to specimens from a non-inflammatory cohort. However, when comparing the data from patients in the malignant and non-malignant cohorts, the individual levels of miR-16, miR-21, and miR-223 showed high variation, without reaching a statistically significant difference. Conclusions: In summary, bile duct stents can be considered as potential sources of intraductal biomarkers, specifically miRNAs. Further profiling and validation analyses are necessary to identify the most appropriate miRNA targets for differentiating bile duct diseases. Full article

Background/Objectives: Early-onset cancer is an emerging global health concern, including in the United States. However, data on early-onset liver and intrahepatic bile duct cancer remain limited. This study aims to fill this gap by analyzing trends in early-onset liver and intrahepatic bile duct cancer in the United States over the past two decades. Methods: This study used National Childhood Cancer Registry data to examine temporal trends in early-onset liver and intrahepatic bile duct cancer in the United States. The analysis involved estimating age-adjusted incidence rates of early-onset liver and intrahepatic bile duct cancer, stratified by histological type, ethnicity, and sex. Results: In 2021, the age-adjusted incidence rate of early-onset liver and intrahepatic bile duct cancer was estimated at 0.53 per 100,000 population (95% Confidence Interval [CI]: 0.48–0.59). From 2001 to 2021, the age-adjusted incidence rate showed a significant annual percent change (APC) of 1.35% (95% CI: 0.87–1.83%). When stratified by sex, the age-adjusted incidence rate in females increased significantly (APC: 3.07%, 95% CI: 2.26–3.87%) while remaining stable in males. Among racial and ethnic groups, non-Hispanic American Indian and Alaska Native (AIAN) individuals had the highest age-adjusted incidence rate, recorded at 2.67 per 100,000 population (95% CI: 0.95–5.85). By histological type, hepatic carcinoma had the highest age-adjusted incidence rate, significantly increasing over time (APC: 1.47%, 95% CI: 0.96–1.99%). In contrast, the incidence rates for hepatoblastoma and unspecified hepatic tumors remained stable between 2001 and 2021. Conclusions: Our study identified an increasing incidence of early-onset liver and intrahepatic bile duct cancer in the United States, primarily driven by cases in females and hepatic carcinoma. Full article

Background: Cholangiocarcinoma, a malignancy originating from the bile ducts, poses significant treatment challenges due to its typically late diagnosis and limited therapeutic options. However, recent advances in molecular genetics enable more personalized treatment approaches. A notable breakthrough in this context is the identification of isocitrate dehydrogenase (IDH) mutations, particularly IDH1 and IDH2, which occur in a subset of cholangiocarcinoma patients. Those with IDH1/2 mutations may benefit from targeted therapies. For instance, Ivosidenib, an IDH1 inhibitor, has shown efficacy in clinical trials, offering a new therapeutic option for patients with IDH1-mutant cholangiocarcinoma. Developing and implementing standardized protocols for testing and reporting mutation status are crucial for consistency and accuracy in clinical practice. Both the Idylla™ IDH1-2 Mutation Assay Kit as a FastTrack method and Next-Generation Sequencing (NGS) panels play critical roles in molecular characterization of cholangiocarcinoma. Methods: Under this aspect, a set of cholangiocarcinomas was tested using the Idylla™ platform regarding the respective recommended guidelines and standards of DIN EN ISO:17020 and DIN EN ISO:15198. Results: Overall, 25 clinically diagnosed intrahepatic cholangiocarcinomas or Adeno-CUPs were analyzed. IDH1/2 mutations were identified in 68% (17/25) of cases using both methods, with high concordance between NGS and Idylla™ results. Discrepancies were observed in two samples, where Idylla™ detected no mutations, but NGS reported IDH1 and IDH2 mutations, respectively. Conclusions: Idylla^TM offers a rapid, user-friendly, and specific method for detecting IDH1/2 mutations, ideal for immediate clinical needs. NGS, while more time-consuming and costly, provides comprehensive genetic profiles valuable for personalized medicine and research. The choice between these methods should be guided by the clinical context, resource availability, and individual patient needs. For routine diagnostics, we recommend an algorithmic approach starting with the FastTrack method followed by NGS for wildtype cases. Full article

Mucinous cystic neoplasm of the liver (MCN-L) is a rare benign tumor accounting for less than 5% of all liver cysts, with MCN-L in the hilar region being exceptionally uncommon and often misdiagnosed due to its complex presentation. A 48-year-old woman presented with obstructive jaundice following initial laparoscopic drainage of hepatic cysts, where pathology initially indicated benign cystic lesions. Months later, imaging revealed an enlarged cystic lesion in the left liver lobe with intrahepatic bile duct dilation. Further evaluations, including ultrasound, enhanced CT, and MRI, confirmed a large cystic lesion compressing the intrahepatic bile ducts. After a multidisciplinary discussion, hepatic cyst puncture and drainage were performed, temporarily alleviating jaundice. However, she returned with yellowish-brown drainage fluid and worsening jaundice, prompting cyst wall resection. Postoperative pathology confirmed MCN-L. Three months later, jaundice subsided, and a hepatic resection of segment 4 was performed, with pathology confirming low-grade MCN-L. At a 12-month follow-up, the patient showed no abnormalities. This case highlights the diagnostic and therapeutic challenges of MCN-L in the hilar region, as it can easily be mistaken for other liver cystic lesions on imaging. Pathologic examination is essential for definitive diagnosis, and early radical surgical resection is critical to improve prognosis and reduce the risk of malignancy and recurrence. Full article

Background and Aims: Primary biliary cholangitis (PBC) leads to the slow, progressive destruction of the small bile ducts with consecutive cholestasis and intrahepatic cholangitis. If this disease remains untreated, liver parenchyma will be damaged resulting in fibrosis and end-stage liver disease with the need for transplantation. The approval of the Farnesoid X receptor agonist obeticholic acid (Ocaliva; OCA) in early 2017 expanded the drug therapy options of PBC, which previously consisted primarily of the administration of ursodeoxycholic acid (UDCA). Patients and Methods: Included in our prospective pilot study were 16 patients with a confirmed diagnosis of PBC who were treated with an add-on therapy with OCA (5 mg/d). None of the patients had an overlap to autoimmune hepatitis. Patients were investigated between 09/2022 and 09/2023. Results: The majority of patients was female (15/16, 93.75%), and the mean age was 57.63 ± 9.59 (43–77) years. OCA treatment led to a statistically significant decrease in aspartate aminotransferase (AST; AST baseline: 38.50 [26.25; 50.00] IU/L vs. AST 6-month follow-up: 23.50 [21.50; 44.25] IU/L, p = 0.0012), alanine aminotransferase (ALT; ALT baseline: 55.50 [28.75; 97.00] IU/L vs. ALT 6-month follow-up: 36.50 [28.00; 57.25] IU/L, p = 0.0035), and gamma-glutamyl transferase (GGT; GGT baseline: 168.00 [100.30; 328.50] IU/L vs. GGT 6-month follow-up: 88.00 [44.50; 259.80] IU/L, p = 0.0063), while the decrease in alkaline phosphatase (AP) was not statistically significant (AP baseline: 197.00 [170.00; 253.30] IU/L vs. AP 6-month follow-up: 196.00 [134.00; 227.00] IU/L, p = 0.0915). In addition, liver stiffness measurement (LSM) showed a statistically significant decrease after six months of treatment with OCA (LSM baseline: 7.85 [5.55; 10.13] kPa vs. LSM 6-month follow-up: 5.95 [4.55; 8.225] kPa, p = 0.0001). However, the increase in enzymatic liver function measured by LiMAx failed to reach statistical significance, but showed a positive trend (LiMAx baseline: 402.50 [341.50; 469.80] μg/kg/h vs. LiMAx 6-month follow-up: 452.50 [412.50; 562.00] μg/kg/h, p = 0.0625). In none of our patients did therapy with obeticholic acid have to be stopped due to pruritus or poor tolerability. Conclusions: In patients with PBC without adequate response to UDCA, OCA is a promising alternative, which in our group of 16 patients led to a significant improvement of liver enzymes, the amelioration of liver fibrosis, and an increase in liver function capacity in a short-term clinical course. Full article

Background/objectives: The real-world survival of patients with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib has been explored retrospectively with a small sample size. We conducted a prospective observational 2-year extension study (510 study) of a 1-year observational post-marketing study of lenvatinib (504 study) to evaluate the long-term overall survival (OS) of patients with uHCC treated with lenvatinib and associated factors with a large sample size. Methods: Patients with uHCC included (July 2018 to January 2019) in the 504 study and who consented were eligible for the 510 study and were followed for up to 3 years after lenvatinib treatment initiation. Using the data from the 504 study and 510 study of the 504 study analysis set, we estimated the OS, the time from the first lenvatinib dose to all-cause death by the Kaplan–Meier method (ClinicalTrials.Gov Registration ID, 504 study: NCT03663114; 510 study: NCT04008082). Results: The 703 patients included in the analysis were followed for a median period (min, max) of 12.5 months (0.1, 44.8). The median OS (95% confidence interval) was 16.6 months (15.4, 18.5). OS was significantly (p < 0.05) associated with bile duct invasion (hazard ratio [HR]: 1.621), portal vein invasion (HR: 1.365), ≥ 4 intrahepatic lesions (HR: 1.437), extrahepatic lesions (HR: 1.357), Child–Pugh B/C (HR: 1.515), mALBI Grade 2a (HR: 1.331), and Grade ≥ 2b (HR: 1.811). Conclusions: This large-scale, prospective, real-world study demonstrated a long OS, comparable to that reported in the global Phase III REFLECT trial. More advanced-stage tumors and worse hepatic function have been suggested as OS-associated factors, consistent with previous reports. Full article

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care. Full article

Objectives: In hepatopancreatic diseases, stenting is widely employed to manage cholangitis and obstructive jaundice. Stent materials are primarily categorized as plastic or metal. Plastic stents have notable advantages, such as reduced likelihood of peripheral bile duct obstruction, a lower cost, and the ease of replacement compared to metallic stents. However, their patency period is shorter due to narrower diameters. Plastic stents are typically composed of materials like polyurethane or polyethylene. To improve patency, new dual-layer stents combine polyurethane with polytetrafluoroethylene (PTFE). PTFE, used in the inner layer, is expected to prevent biofilm formation. This study aimed to assess the clinical efficacy of this dual-layer stent. Methods: A retrospective analysis was performed on 48 cases (Group R) using REGULUS^® from November 2022 to November 2023 and 30 cases (Group IS) using inside-type plastic stents from January 2020 to November 2023 for malignant hilar and intrahepatic bile duct obstructions. Stent patency and clinical outcomes were compared between the groups. Results: There was no significant difference in the recurrent biliary obstruction (RBO) rate between the groups (p = 0.644). The time to recurrent biliary obstruction (TRBO) was 74 days in Group R and 118 days in Group IS, with no significant difference (p = 0.219). Conclusions: The dual-layer stent placed across the papilla demonstrated comparable clinical outcomes to inside-type stents. The PTFE inner layer likely reduces biofilm formation, enhancing patency. Across-the-papilla placement may facilitate reinterventions in challenging cases, broadening stent options. Full article

Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000–20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g., isolated, Biliary Atresia Splenic Malformation syndrome, Cat-eye syndrome, cystic BA, and CMV-associated BA). Facts about its aetiology are hard to encounter but might include genetic, developmental, exposure to an environmental toxin, or perinatal virus infection. However, the cholestatic injury triggers an intrahepatic fibrotic process beginning at birth and culminating in cirrhosis some months later. Affected infants present with a triad of conjugated jaundice, pale stools, and dark urine and may have hepatosplenomegaly upon examination, with later ascites coincident with the onset of progressive liver disease. Rapid, efficient, and expeditious diagnosis is essential with the initial treatment being surgical, typically with an attempt to restore the bile flow (Kasai portoenterostomy (KPE)) or primary liver transplantation (<5%) if considered futile. Failure to restore bile drainage or the onset of complications such as recurrent cholangitis, treatment-resistant varices, ascites, hepatopulmonary syndrome, and occasionally malignant change are usually managed by secondary liver transplantation. This issue summarises recent advances in the disease and points a way to future improvements in its treatment. Full article