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Noninvasive visualization of the biliary tree is of paramount importance in any patient who may require a biliary surgical intervention. Most hospitals and imaging centers offer ultrasound, computed tomography (CT), cholescintigraphy (commonly known as hepatobiliary iminodiacetic acid scan), and MRI whenever acute biliary pathology is suspected. PET combined with CT is sometimes utilized to evaluate biliary malignancy and metastatic disease. Unfortunately, these imaging modalities are often ordered incorrectly and have numerous limitations. This article discusses the strengths and weaknesses or each imaging modality and focuses on appropriateness of their utilization in clinical practice., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies., Methods: We evaluated 93 cases-20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas-for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls., Results: Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P  > .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases., Conclusions: Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell's original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

Non-iatrogenic traumatic bile duct injuries (NI-TBIs) are a rare complication after abdominal trauma, with an estimated prevalence of 2.8-7.4% in patients underwent blunt liver injuries. They may be overlooked in patients with extensive multi-organ trauma, particularly hepatic, splenic and duodenal injuries, which have a prevalence of 91%, 54% and 54%, respectively. Whole body contrast-enhanced computed tomography (CE-CT) represents the examination of choice in polytraumatized hemodynamically stable patients, as it allows a comprehensive evaluation of vascular, parenchymal, bone and soft tissues injuries, but the diagnosis of any biliary leaks is limited to the evaluation of nonspecific imaging findings and on findings evolution in the follow-up, such as the progressive growth of fluid collections. Furthermore, biliary complications, such as the occurrence of biloma or biliary peritonitis, may become manifest several days after the initial trauma, often with unspecific progressive signs and symptoms. Although CT and ultrasonography can suggest bile leaks based on several nonspecific imaging findings (e.g., fluid collections), magnetic resonance imaging (MRI) using hepatobiliary contrast agents helps to identify the site and entity of post-traumatic biliary disruption. Indeed, MRI allows to obtain cholangiographic sequences that may show post-traumatic active bile leakage and cysto-biliary communications by direct visualisation of contrast material extravasation into fluid collections, increasing the preoperative accuracy of NI-TBIs. Few data are available about MRI use in the follow-up of trauma with NI-TBI management. So, in the present mini review, its role is reviewed and our preliminary experience in this field is reported., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-29/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Anatomy has remained an interest of physicians throughout the ages. The biliary tract spans from the liver to the hepatoduodenal mesentery, pancreas, and into the duodenum. Therefore, it is important for not only hepatobiliary surgeons but also general gastrointestinal surgeons, gastroenterologists, radiologists, and pathologists to be familiar with biliary anatomy and its variants. While surgery for hilar cholangiocarcinoma is one of the most challenging procedures, cholecystectomy is one of the most common procedures done from the beginning of surgical training. We hope that by answering the following questions, you will gain a comprehensive understanding of biliary anatomy and a greater appreciation for it., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: A choledochal cyst is a cystic dilatation of the biliary tree, also termed a biliary cyst, including an intrahepatic cyst as well. Magnetic resonance cholangiopancreatography (MRCP) is the gold standard investigation of choice for this pathology. Todani classification is most commonly used to classify choledochal cysts., Materials and Methods: A total of 30 adult patients with choledochal cysts presenting at our center from December 1, 2009, to October 31, 2019, were studied retrospectively., Results: The mean age was 35.13 years ranging from 18 to 62 years with a male-to-female ratio of 1:3.29. Of the patients, 86.6% presented with abdominal pain. Total serum bilirubin was raised in six patients with a mean of 1.84 mg/dL. MRCP was done in all patients, which had almost 100% sensitivity. Two cases had anomalous pancreaticobiliary duct union. In our study, we found only type I and type IVA cysts according to the Todani classification (type IA = 56.3%, IB = 11%, 1C = 16%, and IVA = 17%). The mean size of the cyst was 2.37 cm. Complete cyst excision with Roux-en-Y hepaticojejunostomy was performed in all patients. Four patients had surgical site infections and two had bile leaks. One patient developed hepatic artery thrombosis. All complications were eventually managed conservatively. Mortality was nil in our study with the mean postoperative stay being 7.97 days., Conclusion: Adult presentation of biliary cysts is not an uncommon entity in the Indian population and should be considered as a differential diagnosis of biliary pathology in adult patients. Complete excision of cysts with bilioenteric anastomosis is the current treatment of choice., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ranvir et al.)

The gallbladder is not part of the standard survey of a fetus during obstetrical ultrasound. Yet, some anomalies can be detected. Most are clinically benign, but some are features of or associated with more serious complications. Biliary atresia constitutes the diagnosis with the worst prognosis. Its in utero diagnosis is difficult. Still, markers do exist and should be searched for. Knowledge of the normal appearances, variants and abnormalities of the gallbladder contributes to proper management. Any suspicion should lead to meticulous postnatal workup. Pre- or postnatal magnetic resonance imaging can provide additional information in select cases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs., Methods: PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random-effects model., Results: Eight observational studies (3 cohort and 5 case-control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0-71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51-0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38-0.94) and GBC was 0.78 (95% CI: 0.68-0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66-1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69-0.88) and 0.70 (95% CI: 0.61-0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non-steroidal anti-inflammatory drugs (aRR: 0.80, 95% CI: 0.72-0.89) and metformin (aRR: 0.80, 95% CI: 0.72-0.90)., Conclusions: Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The biliary system is a highly branched tubular network consisting of intrahepatic bile ducts (IHBDs) and extrahepatic bile ducts (EHBDs). IHBDs are derived from hepatic progenitor cells, while EHBDs originate directly from the endoderm through a separate branching morphogenetic process. Traits that are important for cancer are often found to overlap in developmental and other processes. Therefore, it has been suggested that intrahepatic cholangiocarcinomas (iCCAs) and extrahepatic cholangiocarcinomas (eCCAs) have different developmental mechanisms. While much evidence is being gathered on the mechanism of iCCAs, the evidence for eCCA is still very limited. The main reason for this is that there are very few appropriate animal models for eCCA. We can gain important insights from these animal models, particularly genetically engineered mouse models (GEMMs). GEMMs are immunocompetent and mimic human CCA subtypes with a specific mutational pattern, allowing the development of precancerous lesions, that is, biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB). This review provides a summary of the pathogenesis and mechanisms of eCCA that can be revealed by GEMMs. Furthermore, we discuss several clinical questions, such as whether BilIN and IPNB really become malignant, whether the peribiliary gland is the origin of eCCAs, and others., (© 2022 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin., Case Presentation: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this is one of the more time-sensitive diagnoses that must be made in neonates with conjugated hyperbilirubinemia. He was ultimately found to have choledocholithiasis on magnetic resonance cholangiopancreatography. He was managed conservatively with optimizing nutrition and ursodeoxycholic acid therapy., Conclusions: We found that conservative management, specifically optimizing nutrition and treating with ursodeoxycholic acid, can be a sufficient approach to facilitating resolution of the choledocholithiasis and conjugated hyperbilirubinemia., (© 2022. The Author(s).)

Patch grafting, a novel strategy for transplantation of stem/progenitor organoids into porcine livers, has been found successful also for organoid transplantation into other normal or diseased solid organs in pigs and mice. Each organoid contained ∼100 cells comprised of biliary tree stem cells (BTSCs), co-hepato/pancreatic stem/progenitors, and partnered with early lineage stage mesenchymal cells (ELSMCs), angioblasts and precursors to endothelia and stellate cells. Patch grafting enabled transplantation into livers or pancreases of ≥10 8th (pigs) or ≥10 6th-7th (mice) organoids/patch. Graft conditions fostered expression of multiple matrix-metalloproteinases (MMPs), especially secretory isoforms, resulting in transient loss of the organ's matrix-dictated histological features, including organ capsules, and correlated with rapid integration within a week of organoids throughout the organs and without emboli or ectopic cell distribution. Secondarily, within another week, there was clearance of graft biomaterials, followed by muted expression of MMPs, restoration of matrix-dictated histology, and maturation of donor cells to functional adult fates. The ability of patch grafts of organoids to rescue hosts from genetic-based disease states was demonstrated with grafts of BTSC/ELSMC organoids on livers, able to rescue NRG/FAH-KO mice from type I tyrosinemia, a disease caused by absence of fumaryl acetoacetate hydrolase. With the same grafts, if on pancreas, they were able to rescue NRG/Akita mice from type I diabetes, caused by a mutation in the insulin 2 gene. The potential of patch grafting for cell therapies for solid organs now requires translational studies to enable its adaptation and uses for clinical programs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Obstructive cholestasis can lead to significant alterations of the biliary tree depending on the extent and duration of the biliary occlusion. Current experimental studies reported about advanced techniques for corrosion cast and 3D reconstruction (3D-reco) visualizing delicate microvascular structures in animals. We compared these two different techniques for visualization and quantitative assessment of the obstructed murine biliary tree with classical 2D histology., Methods: Male mice (n = 36) were allocated to 3 different experiments. In experiments 1 and 2, we injected two different media (Microfil© for 3D-reco, MV; Batson's No.17 for corrosion cast, CC) into the extrahepatic bile duct. In experiment 3 we sampled liver tissue for 2D histology (HE, BrdU). Time points of interest were days 1, 3, 5, 7, 14, and 28 after biliary occlusion. We used different types of software for quantification of the different samples: IMALYTICS Preclinical for 3D scans (MV); NDP.view2 for the digital photography of CC; HistoKat software for 2D histology., Results: We achieved samples in 75% of the animals suitable for evaluation (MV and CC, each with 9/12). Contrasting of terminal bile ducts (4th order of branches) was achieved with either technique. MV permitted a fast 3D-reco of the hierarchy of the biliary tree, including the 3rd and 4th order of branches in almost all samples (8/9 and 6/9). CC enabled focused evaluation of the hierarchy of the biliary tree, including the 4th to 5th order of branches in almost all samples (9/9 and 8/9). In addition, we detected dense meshes of the smallest bile ducts in almost all CC samples (8/9). MV and CC allowed a quantitative assessment of anatomical details of the 3rd and 4th order branches of almost every sample. The 2D histology identified different kinetics and areas of proliferation of hepatocytes and cholangiocytes. Complementary usage of 3D-reco, corrosion casting and 2D histology matched dense meshes of small bile ducts with areas of intensive proliferative activity of cholangiocytes as periportal proliferative areas of 4th and 5th order branches (∼terminal bile ducts and bile ductules) matched with its morphological information the matching assessment of areas with increased proliferative activity (BrdU) and a partial quantification of the characteristics of the 4th order branches of the biliary tree., Conclusion: The 3D-reco and corrosion casting of the murine biliary tree are feasible and provide a straightforward, robust, and reliable (and more economical) procedure for the visualization and quantitative assessment of architectural alterations, in comparative usage with the 2D histology., (© 2021 Indian National Association for Study of the Liver.)

Purpose: To compare quantitative biliary measurements obtained with three different magnetic resonance cholangiopancreatography (MRCP) acquisition methods., Methods: This retrospective study was IRB-approved. Patients with combinations of clinically indicated 3D FSE MRCP with sensitivity encoding (SENSE), 3D FSE SENSE MRCP with compressed sensing (CS-FSE; acceleration factor 8), and 3D gradient and spin-echo (GRASE) MRCP, acquired between October 2018 and March 2020, were included. The MRCP + Tuning Threshold algorithm (Perspectum Ltd., Oxford, UK) was used to segment 3D biliary models from MRCP data, with multiple metrics quantified from the models. Single measure, two-way, mixed-effects intra-class correlations, Bland-Altman analyses, and Wilcoxon signed-rank tests were used to compare quantitative measurements., Results: From 160 MRCP datasets (25 3D FSE, 67 3D CS-FSE, 68 3D GRASE) in 69 patients, 48 datasets (7 [28%] 3D FSE, 14 [21%] 3D CS-FSE, 27 [40%] 3D GRASE) failed post-processing due to motion artifacts. The remaining 112 MRCP datasets (18 3D FSE, 53 3D CS-FSE, 41 3D GRASE) from 60 patients were included in the analysis. There was good to excellent agreement between 3D FSE and 3D CS-FSE MRCP for diameter of the left and right hepatic ducts, biliary volume, number and length of ducts, and total length of dilations (ICC: 0.83-0.93). The only metrics that exhibited good agreement between 3D FSE and 3D GRASE MRCP were biliary volume (ICC: 0.75) and total number of dilations (ICC: 0.77)., Conclusion: 3D CS-FSE MRCP produces comparable biliary diameter metrics and global duct quantification to 3D FSE MRCP at a significantly reduced acquisition time., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Cholangiocytes, biliary epithelial cells, are known to spontaneously self-organize into spherical cysts with a central lumen. In this work, we explore a promising biocompatible stereolithographic approach to encapsulate cholangiocytes into geometrically controlled 3D hydrogel structures to guide them towards the formation of branched tubular networks. We demonstrate that within the appropriate mix of hydrogels, normal rat cholangiocytes can proliferate, migrate, and organize into branched tubular structures with walls consisting of a cell monolayer, transport fluorescent dyes into the luminal space, and show markers of epithelial maturation such as primary cilia and continuous tight junctions. The resulting structures have dimensions typically found in the intralobular and intrahepatic biliary tree and are stable for weeks, without any requirement of bulk supporting material, thereby offering total access to the external side of these biliary epithelial constructs., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflict of interest The authors of this study have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details.

Epithelial cell therapies have been at an impasse because of inefficient methods of transplantation to solid organs. Patch grafting strategies were established enabling transplantation of ≥10 7th organoids/patch of porcine GFP+ biliary tree stem/progenitors into livers of wild type hosts. Grafts consisted of organoids embedded in soft (~100 Pa) hyaluronan hydrogels, both prepared in serum-free Kubota's Medium; placed against target sites; covered with a silk backing impregnated with more rigid hyaluronan hydrogels (~700 Pa); and use of the backing to tether grafts with sutures or glue to target sites. Hyaluronan coatings (~200-300 Pa) onto the serosal surface of the graft served to minimize adhesions with neighboring organs. The organ's clearance of hyaluronans enabled restoration of tissue-specific paracrine and systemic signaling, resulting in return of normal hepatic histology, with donor parenchymal cells uniformly integrated amidst host cells and that had differentiated to mature hepatocytes and cholangiocytes. Grafts containing donor mature hepatocytes, partnered with endothelia, and in the same graft biomaterials as for stem/progenitor organoids, did not engraft. Engraftment occurred if porcine liver-derived mesenchymal stem cells (MSCs) were co-transplanted with donor mature cells. RNA-seq analyses revealed that engraftment correlated with expression of matrix-metalloproteinases (MMPs), especially secreted isoforms that were found expressed strongly by organoids, less so by MSCs, and minimally, if at all, by adult cells. Engraftment with patch grafting strategies occurred without evidence of emboli or ectopic cell distribution. It was successful with stem/progenitor organoids or with cells with a source(s) of secreted MMP isoforms and offers significant potential for enabling cell therapies for solid organs., (Copyright © 2021. Published by Elsevier Ltd.)

The study of the fractal architecture of various organs and structures expanded the possibilities for determining the ranges of their functioning and structural arrangement, which, as a result, was reflected in the development of new approaches to diagnostics and therapeutic impacts. The architecture of the excretory duct systems, similar to the hemo- and lymph- circulatory beds and the bronchial tree, is considered fractal. At the same time, information about hitherto unknown structures of the biliary tree continues to appear in the literature. We aimed to study the features of the spatial geometry of the biliary tree and assess the significance of both its fractal and Euclidean characteristics for the development of approaches that facilitate comprehensive description of intrahepatic biliary tract architecture. We investigated the architecture of the biliary trees of six men, seven male canines, and seven male Wistar rats using the corrosion casting method. Corrosion casts were prepared by injecting solidifying latexes into the bile ducts. The preparations were studied using a light stereomicroscope and a scanning electron microscope. Biliary tree branching is of various types. In addition, the correlation between variations in the caliber and length of the bile ducts and their order is not significant. Therefore, the biliary tree should not be considered as a classical fractal and it consists of the main modules, represented by the network of the bile canaliculi (first nonfractal module) and a biliary tree with a fractal branching (second module) that drains the bile canaliculi mesh and the additional modules represented by the mucosal biliary glands (in mammals with the gallbladder) or the periportal biliary plexus (in mammals without a gallbladder) and the aberrant biliary ducts. Such a configuration of the biliary bed should optimally ensure the smooth implementation of the physiological function of the liver, as well as its adaptation to different pathologies accompanied by biliary hypertension. It also might be considered in the diagnosis and assessment of ductular reaction, biliary regeneration, and/or carcinogenesis., (© 2021 Anatomical Society.)

Background: The aim of this study was to present a percutaneous transhepatic biliary puncture simulator that can be used without radiation exposure and that reflects the conventional anatomy of the biliary ducts and its vicinity structures., Methods: An anatomically based model of the biliary tree was developed using a cord network fixed to a wooden frame. The skin, ribs, intercostal muscles, and right lower lobe pleura were simulated using foam sponge, plastic tubes, a polystyrene foam panel, and an air pad, respectively. For the puncture, we used a 20-G Chiba needle and a wire with distal double arches; these were used to troll a cord, simulating the successful puncture of a bile duct. A camera was also placed above the model to allow the trainees to train eye-hand coordination while viewing the image on a monitor in real time. The simulator was tested with 60 radiology residents to evaluate the confidence and skills transferability of the training model., Results: After receiving an introduction of the system and 5 min of training under tutor surveillance, all participants were able to troll a cord of the biliary simulator by themselves in less than 4 min. Only one participant punctured the simulated pleura. The participants' evaluations showed positive results, with increased user confidence and skills transferability after the training session., Conclusions: This proposed simulator can be an effective tool to improve a trainee's confidence and competence while achieving procedural and non-procedural interventional radiology skills related to the liver., Trial Registration: Retrospectively registered., (© 2021. The Author(s).)

The pathological spectrum of intraductal papillary neoplasm of bile duct (IPNB) remains to be clarified. A total of 186 IPNBs were pathologically examined using the type 1 and 2 subclassifications proposed by Japanese and Korean biliary pathologists incorporating a two-tiered grading system (low-grade and high-grade dysplasia), with reference to four subtypes (intestinal [i], gastric [g], pancreatobiliary [pb], and concocytic [o] subtype). IPNBs were classifiable into type 1 composed of low-grade dysplasia and 'high-grade dysplasia with regular structures' (69 IPNBs), and type 2 of 'high grade dysplasia with irregular structures and complicated lesions' (117 IPNBs). Type 1 was more common in the intrahepatic bile duct (78%), whereas type 2 was frequently located in the extrahepatic bile duct (58%). Mucin hypersecretion was more common in type 1 (61%) than in type 2 (37%). IPNBs were classifiable into the four subtypes: 86 iPNBs, 40 gIPNBs, 31 pbIPNBs, and 29 oIPNBs. The four subtypes were histologically evaluable with reference to the type 1 and 2 subclassifications. iIPNB and pbIPNBs were frequently classified as type 2, whereas types 1 and 2 were observed at similar rates in gIPNB and oIPNB. Stromal invasion was almost absent in type 1, irrespective of subtype, but was found in 66 of 117 type 2 IPNBs (P < .01), and postoperative outcome was favorable in IPNBs without invasion compared with IPNBs with invasion (P < .05). The type 1 and 2 subclassifications with reference to the four subtypes may provide useful information for understanding IPNB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Importance: Biliary tree neuroendocrine tumors (NET) are rare, with 100 cases in the literature, and have an excellent prognosis. Although they are rarely diagnosed before surgery, complete surgical excision offers optimal treatment., Case Presentation: We report a case of a 36-year-old female patient referred to the surgical team with obstructive jaundice for which she was investigated and found to have a common bile duct tumor showing proximal obstruction. Excision of the tumor with hepaticojejunostomy was done. Later on, the pathology report showed grade-1, well-differentiated neuroendocrine carcinoma, which was completely excised. No further intervention was provided to the patient., Clinical Discussion: Complete surgical resection with excision of the extrahepatic bile ducts and portal lymphadenectomy in addition to Roux-en-Y hepaticojejunostomy or even pancreaticoduodenectomy for distal CBD neuroendocrine tumors gives sufficient treatment in the majority of cases. No evidence of the advantage of chemo-radiotherapy as part of the treatment for this tumor., Conclusion: Biliary tree neuroendocrine tumors are benign tumors, and it is usually difficult to ascertain the diagnosis preoperatively. However, complete surgical excision offers an optimal treatment with no evidence of chemotherapy or radiotherapy's role in the management., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction Hepatobiliary tree variant anatomy is crucial to understand the preoperative planning of hepatobiliary surgeries. Although the presence of variant anatomy is not an absolute contraindication for liver transplantation, inadvertent mapping can lead to postoperative biliary complications. These variants are also important to be recognized in various hepatobiliary surgeries and interventional procedures. Magnetic resonance cholangiopancreatography (MRCP) is an excellent non-invasive imaging tool that can identify biliary anatomy. The purpose of the current study is focused on determining anatomical variants of the biliary tree on MRCP in our population visiting a teaching hospital in Karachi. Methods This cross-sectional study was conducted on patients referred to Dr. Ziauddin Hospital for MRCP. MRCP was performed on MAGNETOM Avanto, SIEMENS, Belgium, Germany. Images were analyzed on a workstation by two radiologists and a postgraduate trainee. A senior radiologist reviewed equivocal cases. SPSS 22.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. Chi-square test was used to see the link between anatomical variants of biliary tree and gender. P-value of ≤0.05 was considered as statistically significant. Results We recruited 369 patients undergoing MRCP consecutively for our study. Out of 369, 342 patients were eligible for analysis (139 males and 203 females). Standard anatomy was found to be prevalent in 65.8%. Type 3 was the leading variant. A statistically significant difference was recorded for the type 2 anatomic variant which was more frequent in males than females (p-value <0.001), while types 1, 3, and 4 anatomic variants were found to be more in females than males but this difference was not statistically significant. Few other variants were also recorded. Conclusion This study is robust evidence regarding biliary variants in Pakistan. It is important to consider these variants in our region, owing to an increased trend of liver transplants and other hepatobiliary procedures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Naeem et al.)

Intraductal papillary neoplasm of the bile duct (IPNB), a pre-invasive neoplasm of the bile duct, is being established pathologically as a precursor lesion of invasive cholangiocarcinoma (CCA), and at the time of surgical resection, approximately half of IPNBs show stromal invasion (IPNB associated with invasive carcinoma). IPNB can involve any part of the biliary tree. IPNB shows grossly visible, exophytic growth in a dilated bile duct lumen, with histologically villous/papillary neoplastic epithelia with tubular components covering fine fibrovascular stalks. Interestingly, IPNB can be classified into four subtypes (intestinal, gastric, pancreatobiliary and oncocytic), similar to intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNBs are classified into low-grade and high-grade based on lining epithelial features. The new subclassification of IPNB into types 1 (low-grade dysplasia and high-grade dysplasia with regular architecture) and 2 (high-grade dysplasia with irregular architecture) proposed by the Japan-Korea pathologist group may be useful in the clinical field. The outcome of post-operative IPNBs is more favorable in type 1 than type 2. Recent genetic studies using next-generation sequencing have demonstrated the existence of several groups of mutations of genes: (i) IPNB showing mutations in KRAS , GNAS and RNF43 belonged to type 1, particularly the intestinal subtype, similar to the mutation patterns of IPMN; (ii) IPNB showing mutations in CTNNB1 and lacking mutations in KRAS , GNAS and RNF43 belonged to the pancreatobiliary subtype but differed from IPMN. IPNB showing mutation of TP53 , SMAD4 and PIK3CA might reflect complicated and other features characterizing type 2. The recent recognition of IPNBs may facilitate further clinical and basic studies of CCA with respect to the pre-invasive and early invasive stages., Competing Interests: The authors declare no conflict of interest.

Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy, due to complex interactions between the body's immune system and malignant neoplasm. Cholangiocarcinoma (CCA) is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes. These syndromes can present as dermatological, neurological, renal, hematological, or multi-systemic manifestations. Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA. The management plan remains the removal of the underlying cause which in this case is CCA., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: An aberrant biliary duct of segment 5 (B5) is a rare anomaly of the biliary tract. All anatomical anomalies of the biliary tract are risk factors for bile duct injury during surgery. We report a case of cholelithiasis with an aberrant B5 that was detected during a detailed preoperative imaging examination and treated with laparoscopic cholecystectomy., Case Presentation: A 69-year-old woman was admitted to the emergency room of our hospital with abdominal pain. She was diagnosed with cholelithiasis, and an aberrant B5 branching off the hepatic duct was suggested during preoperative imaging. Laparoscopic cholecystectomy was performed at our surgical department. There were no intra- or postoperative complications, and the patient was discharged on the fourth day after surgery., Conclusions: Laparoscopic cholecystectomy can be safely performed without intra- or postoperative complications in patients with cholelithiasis and an aberrant B5 if it is accurately diagnosed preoperatively.

In normal human livers, EpCAM pos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAM pos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAM pos progenitor cells within bile ductules are engaged in driving regenerative processes in chronic diseases affecting hepatocytes or interlobular bile ducts. The EpCAM pos population within peribiliary glands is activated when regenerative needs are finalized to repair large intra- or extra-hepatic bile ducts affected by chronic pathologies, including primary sclerosing cholangitis and ischemia-induced cholangiopathies after orthotopic liver transplantation. Finally, the presence of distinct EpCAM pos cell populations may explain the histological and molecular heterogeneity characterizing cholangiocarcinoma, based on the concept of multiple candidate cells of origin. This review aimed to describe the precise anatomical distribution of EpCAM pos populations within the liver and the biliary tree and to discuss their contribution in the pathophysiology of human liver diseases, as well as their potential role in regenerative medicine of the liver., (Copyright © 2020 Safarikia, Carpino, Overi, Cardinale, Venere, Franchitto, Onori, Alvaro and Gaudio.)

Background/aim: Biliary tree and pancreatic duct can appear in different variations whose proper understanding is obligatory for surgeons. Magnetic resonance cholangiopancreatography (MRCP) is considered a safe and accurate tool for evaluating biliary tree and pancreatic duct. Typical anatomy for right hepatic duct (RHD) and left hepatic duct (LHD) is reported as 57% and 63%, respectively. The most common (4-10%) pancreatic anomaly is divisum. In the present study, we evaluated and determined the prevalence of biliary tree and pancreatic duct variations among patients at a university hospital., Materials and Methods: The MRCP records of 370 patients from 2015 to 2017 were obtained for cross-sectional study. Images were retrospectively reviewed for variations by two independent senior radiologists. Demographic data were obtained for all the patients. Huang et al. classification was used for RHD and LHD variations. The cystic duct was reported based on its course and insertion pattern. The pancreatic duct was observed for the presence of divisum, its course, and configuration., Results: Three hundred and twenty-five patients were included in the final study. Most commonly observed variant for RHD were A1 (34.2%) and A2 (32.2%). For LHD, B1 (71.4%) was the most common variant. Cystic duct insertion was commonly seen as right lateral insertion (27.7%). Pancreatic divisum was observed in 0.6% of cases. Nationality, origin, and gender-specific variations were obtained., Conclusion: Variations in biliary anatomy and pancreatic duct are very diverse and extend from the intrahepatic biliary system down to the pancreas. Performing a similar study on a larger population is mandatory to illustrate the range of variations present within the community.

Background: The Bismuth-Corlette (BC) classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary tree. As the right hepatic artery crosses just behind the left bile duct, we hypothesized that BC IIIb tumors would have a higher likelihood of local unresectability due to involvement of the contralateral artery., Methods: A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma taken to the operating room for intended curative resection between April 2008 and September 2016. Cases were assigned BC stages based on preoperative imaging., Results: Sixty-eight patients were included in the study. All underwent staging laparoscopy after which 16 cases were aborted for metastatic disease. Of the remaining 52 cases, 14 cases were explored and aborted for locally advanced disease. Thirty-eight underwent attempt at curative resection. After excluding cases aborted for metastatic disease, the chance of proceeding with resection was 55.6% for BC IIIb staged lesions compared to 80.0% of BC IIIa lesions and to 82.4% for BC I-IIIa staged lesions (P < 0.05). About 44.4% of BC IIIb lesions were aborted for locally advanced disease versus 17.6% of remaining BC stages., Conclusions: When hilar cholangiocarcinoma is preoperatively staged as BC IIIb, surgeons should anticipate higher rates of locally unresectable disease, likely involving the right hepatic artery., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Contrast enhanced MRI of the liver provides valuable information in the evaluation of both chronic liver disease and focal liver lesions. Currently, two classes of MRI contrast agents are available for clinical use, namely the extracellular contrast agent (ECA) and the hepatobiliary agent (HBA). The use of appropriate contrast agents for liver MRI requires knowledge of the clinical situation and question to be answered. ECAs have been used for decades since their introduction into clinical practice and provide excellent dynamic phase information that is useful in characterizing focal liver lesions. In the last decade, HBAs, particularly Gadoxetate, have been found useful for characterizing lesions with functioning hepatocytes and more importantly in evaluating the biliary tree. Gadoxetate, however, provides less satisfactory dynamic phase images compared to ECAs, particularly during the arterial phase. In this perspective article, we will discuss the various intravenous contrast agents used for liver MRI and their ideal utilization.

Purpose: Autoimmune liver diseases (AILD), including primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH), have overlapping clinical features but distinct management strategies and outcomes. The purpose of this study was to assess the diagnostic performance of quantitative magnetic resonance cholangiopancreatography (MRCP) parameters for distinguishing PSC/ASC from AIH in children and young adults., Materials and Methods: This IRB-approved, cross-sectional study included participants from an institutional AILD registry that underwent baseline serum liver biochemistry testing and 3D fast spin-echo MRCP. The biliary tree was extracted and modeled from MRCP images using novel proprietary software (MRCP+ ™; Perspectum Diagnostics; Oxford, United Kingdom), and quantitative parameters were generated (e.g., biliary tree volume; number and length of bile ducts, strictures, and dilations; bile duct median/maximum diameters). Mann-Whitney U tests were performed to compare laboratory values and MRCP metrics between patient cohorts (clinical diagnosis of PSC/ASC versus AIH). Receiver operating characteristic (ROC) curves and multivariable logistic regression were used to assess diagnostic performance of serum biochemistry values and MRCP parameters for discriminating PSC/ASC from AIH., Results: Thirty percent (14/47) of MRCP exams failed post-processing due to motion artifact. The remaining 33 patients included 20 males and 13 females, with a mean age of 15.1 ± 3.9 years. Eighteen patients were assigned the clinical diagnosis of PSC or ASC and 15 of AIH. All but one quantitative MRCP parameter were significantly different between cohorts (p < 0.05) and predictive of diagnosis (ROC p < 0.05), including numbers of bile duct strictures (area under curve [AUC] = 0.86, p < 0.0001) and dilations (AUC = 0.87, p < 0.0001) and total length of dilated ducts (AUC = 0.89, p < 0.0001). Laboratory values were not significantly different between cohorts (p > 0.05). The best multivariable model for distinguishing PSC/ASC from AIH included total length of dilated ducts (odds ratio [OR], 1.08; 95% CI 1.02-1.14) and maximum left hepatic duct diameter (OR, 1.21; 95% CI 0.57-2.56) [AUC = 0.92]., Conclusion: Quantitative MRCP parameters provide good discrimination of PSC/ASC from AIH.

Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Background: Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult., Methods: In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry)., Results: Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7-202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45-71) and 47% (34-50), respectively. Patients > 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22-54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery., Conclusion: Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.

The biological behavior of neuroendocrine tumors (NETs) is heterogeneous and differs from that of cholangiocarcinoma, which is the most common malignant tumor of the biliary tree. However, the preoperative diagnosis of NET in the biliary tree is extremely difficult and to our knowledge, diagnosis by brush cytology has not previously been reported. Herein, we first reported a case of biliary NET preoperatively diagnosed by brush cytology in a 33-year-old female patient. Imaging study revealed a 2.6-cm mass in the common hepatic duct. The brush cytology was characterized by loosely cohesive plasmacytoid tumor cells and scattered clusters of thin vascular septa. The tumor cells showed abundant cytoplasm and severe nuclear size variation but mitosis was not observed. Immunohistochemical staining of the cell block (CB) showed strong positivity for both synaptophysin and chromogranin A and a Ki-67 labeling index of 3.5%. The surgically resected bile duct mass was pathologically confirmed as NET, G2 with lymphovascular and perineural invasion of the tumor cells. The patient showed no evidence of tumor recurrence 10 months after operation without adjuvant chemotherapy. Suspicion of this rare tumor and immunohistochemical staining of the CB are important for the preoperative diagnosis of NET in the biliary tree., (© 2019 Wiley Periodicals, Inc.)

Practical Relevance: Abdominal ultrasound plays a vital role in the diagnostic work-up of many cats presenting to general and specialist practitioners. The biliary tree encompasses the liver, gall bladder and bile ducts, although only diseases affecting the latter two are discussed here. Diseases of the bile ducts and gall bladder are more common than those of the liver parenchyma and ultrasound plays an important role in their diagnosis., Clinical Challenges: Despite ultrasonography being a commonly used modality, many practitioners are not comfortable performing an ultrasound examination or interpreting the resulting images. Even differentiating between normal variation and pathological changes can be challenging for all but the most experienced. In addition, a lack of pathological change does not necessarily rule out disease; for example, absence of gall bladder and/or extrahepatic biliary distension is not sufficient to exclude the possibility of biliary obstruction, and in many cases of cholangitis the liver and biliary tree are unremarkable on ultrasound examination., Equipment: Ultrasound facilities are readily available to most practitioners, although use of ultrasonography as a diagnostic tool is highly dependent on operator experience., Aim: This review, part of an occasional series on feline abdominal ultrasonography, discusses the appearance of the normal and diseased biliary system. It is aimed at general practitioners who wish to improve their knowledge and confidence in feline abdominal ultrasound and is accompanied by high-resolution images. Percutaneous ultrasound-guided cholecystocentesis is also covered. Ultrasound examination of the liver was discussed in an article published in January 2019 and an upcoming article will cover hepatic vascular anomalies., Evidence Base: Information provided in this article is drawn from the published literature and the author's own clinical experience.

"The anatomy of the biliary tree is notoriously variable. This variation is the bane of the hepatobiliary surgeon, to whom an understanding of biliary anatomic variation is key to the planning and safe conduct of liver surgery, from oncological resections to split-liver transplantation. The hepatic diverticulum, also termed "the liver bud," is the first semblance of the biliary system in the human embryo. A variety of techniques used in the mid twentieth century for imaging the biliary tree have since been abandoned in favor of more practical, safer, less invasive, and more sensitive and specific contemporary methods.", (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies., Competing Interests: The authors declare no conflict of interest.

It has been demonstrated that the liver remarkably alter its tissue structures during regeneration, and various types of liver stem or progenitor cells locating in specific areas in the liver tissue contribute to regeneration. Therefore, it is important to analyze the dynamic rearrangement of the liver tissue structures in 3D for better understanding the process and mechanism of liver regeneration. Here we describe a macroscopic analysis method to visualize the whole 3D structure of the vasculatures and the biliary tree, which are dynamically remodeled during regeneration, and a microscopic analysis method to visualize detailed structures at the cellular level, which can compensate what cannot be detected in the macroscopic analysis.

Calcium (Ca 2+ ) is a versatile second messenger that regulates a number of cellular processes in virtually every type of cell. The inositol 1,4,5-trisphosphate receptor (ITPR) is the only intracellular Ca 2+ release channel in cholangiocytes, and is therefore responsible for Ca 2+ -mediated processes in these cells. This review will discuss the machinery responsible for Ca 2+ signals in these cells, as well as experimental models used to investigate cholangiocyte Ca 2+ signaling. We will also discuss the role of Ca 2+ in the normal and abnormal regulation of secretion and apoptosis in cholangiocytes, two of the best characterized processes mediated by Ca 2+ in this cell type.

Objectives: The palliative treatment of cholangiocarcinoma is based on stent placement with well-known procedure-related complications. Consequently, alternative energy-based techniques were put forward with controversial long-term results. This study aims to evaluate the safety and effectiveness of biliary tree laser ablation (LA) in terms of: (i) absence of perforation, (ii) temperature increase, (iii) induced thermal damage in in vivo models., Materials and Methods: The common bile duct and cystic ducts of two pigs were ablated with a diode laser (circumferential irradiation pattern) for 6 and 3 min at 7 W. Laser settings were chosen from previous ex vivo experiments. Local temperature was monitored through a fibre Bragg grating (FBG) sensor embedded into the laser delivery probe. Histopathological analysis of the ablated specimen was performed through in situ endomicroscopy, haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains., Results: Temperature reached a plateau of 53 °C with consequent thermal damage on the application area, regardless of laser settings and application sites. No perforation was detected macroscopically or microscopically. At the H&E stain, wall integrity was always preserved. The NADH stain allowed to evaluate damage extension. It turned out that the ablation spreading width depended on application time and duct diameter. In situ endomicroscopy revealed a clear distinction between ablated and non-ablated areas., Conclusions: The temperature distribution obtained through LA proved to induce a safe and effective intraductal coagulative necrosis of biliary ducts. These results represent the basis for further experiments on tumour-bearing models for the treatment of obstructive cholangiocarcinoma.

Background: The use of point-of-care ultrasound (POCUS) has become increasingly important in resource-limited settings. It can rapidly diagnose both tropical infectious diseases and more common pathology at the bedside. In these practice settings, POCUS can have a significant impact on management strategies and patient care. Ultrasonography has been the gold standard for the diagnosis and staging of Echinococcus disease. However, even in the "classic" clinical scenario and setting, the clinician must maintain a broad differential diagnosis. Point-of-care ultrasound can be helpful in performing the rapid diagnosis and therefore direct appropriate treatment strategies based on the results., Case Presentation: We present a case of a 27-year-old woman presenting to an emergency department in Peru with jaundice and abdominal pain. Initially given the region of her origin, the working diagnosis was an Echinococcus cyst. However, when POCUS was performed, the findings were not consistent with hydatid disease. Ultimately, surgical pathology revealed a choledochal cyst, a rare finding in adulthood., Conclusions: This case initially appears as a "classic" finding of Echinococcus disease. It is important for the clinician sonographer to appreciate the features consistent with Echinococcus cysts and distinguish from those features that are more consistent with other pathology.

The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines. However, breach of tolerance in the biliary tree results in various cholangiopathies, exemplified by primary biliary cholangitis, primary sclerosing cholangitis and biliary atresia. Lessons learned from immune tolerance of the biliary tree will provide the basis for the development of effective therapeutic approaches against autoimmune biliary tract diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen., (Copyright © 2017 Elsevier B.V. All rights reserved.)