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Clinics in Liver Disease Aug 2022Biliary atresia is a rare disease but remains the most common indication for pediatric liver transplantation as there are no effective medical therapies to slow... (Review)
Review
Biliary atresia is a rare disease but remains the most common indication for pediatric liver transplantation as there are no effective medical therapies to slow progression after diagnosis. Variable contribution of genetic, immune, and environmental factors contributes to disease heterogeneity among patients with biliary atresia. Developing a deeper understanding of the disease mechanism will help to develop targeted medical therapies and improve patient outcomes.
Topics: Biliary Atresia; Child; Humans; Infant; Liver Transplantation
PubMed: 35868678
DOI: 10.1016/j.cld.2022.03.001 -
Seminars in Interventional Radiology Aug 2021The hepatobiliary system is known to have high anatomic variability, as studies have shown variant rates of over 40% among individuals. This review will describe biliary... (Review)
Review
The hepatobiliary system is known to have high anatomic variability, as studies have shown variant rates of over 40% among individuals. This review will describe biliary anatomy and the most common anatomic variants, knowledge of which is critical to ensuring safe and effective biliary interventions.
PubMed: 34393334
DOI: 10.1055/s-0041-1731085 -
Aging May 2023Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also...
BACKGROUND
Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arises in biliary atresia (BA), the first cause of pediatric liver transplantation. Since alternatives to transplantation are needed, our aim was to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis.
METHODS
BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-β-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administrated to two-month-old Wistar rats after bile duct ligation (BDL).
RESULTS
Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and expression) and hepatocytes mass loss ().
CONCLUSIONS
BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.
Topics: Humans; Rats; Animals; Biliary Atresia; Liver Cirrhosis, Biliary; Rats, Wistar; Liver; Hepatocytes; Cellular Senescence
PubMed: 37204430
DOI: 10.18632/aging.204700 -
Hepatology (Baltimore, Md.) Jul 2009
Topics: Humans; Liver Cirrhosis, Biliary
PubMed: 19554543
DOI: 10.1002/hep.22906 -
Seminars in Interventional Radiology Dec 2016Differentiating benign and malignant biliary strictures is a challenging and important clinical scenario. The typical presentation is indolent and involves elevation of... (Review)
Review
Differentiating benign and malignant biliary strictures is a challenging and important clinical scenario. The typical presentation is indolent and involves elevation of liver enzymes, constitutional symptoms, and obstructive jaundice with or without superimposed or recurrent cholangitis. While overall the most common causes of biliary strictures are malignant, including cholangiocarcinoma and pancreatic adenocarcinoma, benign strictures encompass a wide spectrum of etiologies including iatrogenic, autoimmune, infectious, inflammatory, and congenital. Imaging plays a crucial role in evaluating strictures, characterizing their extent, and providing clues to the ultimate source of biliary obstruction. While ultrasound is a good screening tool for biliary ductal dilatation, it is limited by a poor negative predictive value. Magnetic resonance cholangiopancreatography is more than 95% sensitive and specific for detecting biliary strictures with the benefit of precise anatomic localization. Other commonly employed imaging modalities include endoscopic retrograde cholangiopancreatography with endoscopic ultrasound, contrast-enhanced CT, and cholangiography. First-line treatment of benign biliary strictures is endoscopic dilation and stenting. In patients with anatomy that precludes endoscopic cannulation, percutaneous biliary drain insertion and balloon dilation is preferred.
PubMed: 27904249
DOI: 10.1055/s-0036-1592325 -
Seminars in Interventional Radiology Aug 2021Biliary endoscopy is underutilized by interventional radiologists and has the potential to become an effective adjunctive tool to help both diagnose and treat a variety... (Review)
Review
Biliary endoscopy is underutilized by interventional radiologists and has the potential to become an effective adjunctive tool to help both diagnose and treat a variety of biliary pathology. This is particularly true in cases where endoscopic retrograde cholangiopancreatography fails or is not feasible due to surgically altered anatomy. Both preoperative clinical and technical procedural factors must be taken into consideration prior to intervention. In this article, clinical evaluation, perioperative management, and procedural techniques for percutaneous biliary endoscopy are reviewed.
PubMed: 34393344
DOI: 10.1055/s-0041-1731372 -
Seminars in Liver Disease Feb 2017Despite decades of basic research, biliary diseases remain prevalent, highly morbid, and notoriously difficult to treat. We have, however, dramatically increased our... (Review)
Review
Despite decades of basic research, biliary diseases remain prevalent, highly morbid, and notoriously difficult to treat. We have, however, dramatically increased our understanding of biliary developmental biology, cholangiocyte pathophysiology, and the endogenous mechanisms of biliary regeneration and repair. All of this complex and rapidly evolving knowledge coincides with an explosion of new technological advances in the area of regenerative medicine. New breakthroughs such as induced pluripotent stem cells and organoid culture are increasingly being applied to the biliary system; it is only a matter of time until new regenerative therapeutics for the cholangiopathies are unveiled. In this review, the authors integrate what is known about biliary development, regeneration, and repair, and link these conceptual advances to the technological breakthroughs that are collectively driving the emergence of a new global field in biliary regenerative medicine.
Topics: Animals; Biliary Tract; Biliary Tract Diseases; Humans; Liver; Regeneration; Regenerative Medicine; Stem Cells
PubMed: 28201845
DOI: 10.1055/s-0036-1597818 -
Mayo Clinic Proceedings Jan 1998Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many cases, the intrahepatic bile... (Review)
Review
Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many cases, the intrahepatic bile ducts. In the United States, from 400 to 600 new cases of biliary atresia are encountered annually. The diagnosis is usually suggested by the persistence of jaundice for 6 weeks or more after birth. Several factors have been considered for the pathogenesis of extrahepatic biliary atresia, including viral infection, metabolic insults, and abnormalities in bile duct morphogenesis. Although selected patients benefit from prompt diagnosis and Kasai portoenterostomy surgical intervention within the first 60 days of life, many ultimately require liver transplantation because of portal hypertension, recurrent cholangitis, and cirrhosis.
Topics: Bile Ducts, Extrahepatic; Biliary Atresia; Diagnosis, Differential; Humans; Liver
PubMed: 9443685
DOI: 10.1016/S0025-6196(11)63625-2 -
Transplant International : Official... 2022In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies... (Review)
Review
In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.
Topics: Biliary Tract; Biomarkers; Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion
PubMed: 35707635
DOI: 10.3389/ti.2022.10398