Recent advances in understanding biliary atresia

Wehrman, Andrew; Waisbourd‐Zinman, Orith; Wells, Rebecca G.

doi:10.12688/f1000research.16732.1

Cited by 30 publications

(27 citation statements)

References 41 publications

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“…In spite of the enormity of experimental and patient-based mechanistic data generated over the past decades, the challenges of early diagnosis and preventing either the inception or progression of BA still remain unmet linked primarily to unknown etiologies and existence of additional pathways of biliary injury ( 17 ). In parallel, the rarity of BA and the availability of a single animal model that partially recapitulates the spectrum of extrahepatic biliary disease with no liver fibrosis substantially limits the development of newer treatment approaches ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Recent developments in etiology and disease modeling of biliary atresia: a narrative review

et al. 2020

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Biliary atresia (BA) is a rare but severe fibroinflammatory disease of the extrahepatic and the intrahepatic bile ducts. Without prompt interventions, BA has fatal outcomes and is the most common indicator for pediatric liver transplantation (LTx). While the mainstay of treatment involves surgically correcting the extrahepatic biliary obstruction via Kasai hepato-portoenterostomy (KHPE), activation of a multitude of biological pathways and yet-to-be-determined etiology in BA continue to foster liver inflammation, cirrhosis and need for LTx. However, important caveats still exist in our understandings of the biliary pathophysiology, the rapidity of liver fibrosis and progression to liver failure, largely due to limited knowledge of the triggers of biliary injury and the inability to accurately model human BA. Although inconclusive, a large body of existing literature points to a potential viral infection in the early peri- or postnatal period as triggers of epithelial injury that perpetuates the downstream biliary disease. Further confounding this issue, are the lack of in-vivo and in-vitro models to efficiently recapitulate the cardinal features of BA, primarily liver fibrosis. To overcome these barriers in BA research, new directions in recent years have enabled (I) identification of additional triggers of biliary injury linked mostly to environmental toxins, (II) development of models to investigate liver fibrogenesis, and (III) translational research using patient-derived organoids. Here, we discuss recent advances that undoubtedly will stimulate future efforts investigating these new and exciting avenues towards mechanistic and drug discovery efforts and disease-preventive measures. The implications of these emerging scientific investigations and disease modeling in severe fibrosing cholangiopathies like BA are enormous and contribute substantially in our understandings of this rare but deadly disease. These findings are also expected to facilitate expeditious identification of translationally targetable pathways and bring us one step closer in treating an infant with BA, a population highly vulnerable to life-long liver related complications.

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Section: Introductionmentioning

confidence: 99%

Recent developments in etiology and disease modeling of biliary atresia: a narrative review

et al. 2020

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“…The early diagnosis depends on several factors, such as the existence of a screening program, regular postnatal medical surveillance, patient education. For clinical screening, the use of stool cards has been an efficient method to reduce the age at diagnosis [ 5 , 8 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, long-term survival means that patients can reach up to 20-years of age and more [ 7 ]. However, even with the best experience, there are still undetermined processes in the pathophysiology of the disease leading to a high risk of complications which finally require liver transplantation in 30% to 50% of patients [ 8 ]. However, an early timing may be associated with higher operative risks for the small-sized recipients and side-effects of prolonged immunosuppression, while a prolonged waiting time may increase the risk of complications on advanced cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation

et al. 2020

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Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1–4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice’s clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection.

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“…A few familial cases are described and there no increase in the incidence has been note in twins, some investigators pose that BA begins in the uterus. 1,3,5,8,13…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

“…Polymorphisms that enhance expression of the CD14 gene, which plays a role in the recognition of bacterial endotoxin, have been associated with BA and idiopathic neonatal cholestasis. 2,5,6,10,11,17,18 clAssIfIcAtIon based on timing of onset postnatal biliary atresia (65% to 90%): Usually an isolated disease. embryonal or fetal biliary atresia (10% to 35%): Most cases associated with other congenital malformations, may also be associated with cystic dilatation of biliary remnants.…”

Section: Immunologicmentioning

confidence: 99%

Biliary Atresia: A Systematic Review of Etiology, Pathogenesis, Diagnosis and Treatment

Alfonso¹

2020

Gen Surg Open A Open J

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Biliary Atresia (BA) is an uncommon, progressive and idiopathic fibro-obliterative cholangiopathy. The typical clinical features should be identified prompt in order to realize a Kasai Hepatoportoenterostomy (HPE) for restore the bile flow. However, despite HPE the BA remains the most common indication for liver transplantation in children. The lasts studies have shown the importance of virus, immunity and other environmental substances in pathogenesis of BA that is important in order to look for new therapeutic and preventive strategies. This article is a systematic review of the literature about actual evidence in BA. Keywords: Biliary atresia; Neonatal jaundice; Kasai hepatoportoenterostomy; Liver transplantation

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Recent advances in understanding biliary atresia

Cited by 30 publications

References 41 publications

Recent developments in etiology and disease modeling of biliary atresia: a narrative review

Recent developments in etiology and disease modeling of biliary atresia: a narrative review

Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation

Biliary Atresia: A Systematic Review of Etiology, Pathogenesis, Diagnosis and Treatment

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