In Utero Extrahepatic Bile Duct Damage and Repair: Implications for Biliary Atresia.

Biliary atresia (BA) is a cholangiopathy affecting the extrahepatic bile duct (EHBD) of newborns. The etiology and pathophysiology of BA are not fully understood; however, multiple causes of damage and obstruction of the neonatal EHBD have been identified. Initial damage to the EHBD likely occurs before birth.

Conjugated hyperbilirubinemia is associated with increased morbidity and mortality after neonatal heart surgery.

Background: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality.

Methods: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020.

Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers.

Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding of molecular changes in the biliary system during NMP remains incomplete.

Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion.

Background: End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.

Methods: Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial.

Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.

Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase.

Persistent biliary hypoxia and lack of regeneration are key mechanisms in the pathogenesis of posttransplant nonanastomotic strictures.

Background And Aims: Nonanastomotic biliary strictures (NAS) are a major cause of morbidity after orthotopic liver transplantation (OLT). Although ischemic injury of peribiliary glands (PBGs) and peribiliary vascular plexus during OLT has been associated with the later development of NAS, the exact underlying mechanisms remain unclear. We hypothesized that bile ducts of patients with NAS suffer from ongoing biliary hypoxia and lack of regeneration from PBG stem/progenitor cells.

Dual Versus Single Oxygenated Hypothermic Machine Perfusion of Porcine Livers: Impact on Hepatobiliary and Endothelial Cell Injury.

Background: Hypothermic oxygenated machine perfusion (HOPE) reduces ischemia-reperfusion injury of donor livers and is increasingly used in clinical transplantation. However, it remains unclear whether perfusion via the portal vein alone (HOPE) or via both the portal vein and hepatic artery (dual HOPE or DHOPE) is superior.

Methods: Twelve porcine livers donated after circulatory death were randomized for 2 h of HOPE (n = 6) or DHOPE (n = 6), followed by 4 h of warm reperfusion with whole blood, to mimic transplantation.

Evidence for Recipient-Derived Cells in Peribiliary Glands and Biliary Epithelium of the Large Donor Bile Ducts After Liver Transplantation.

Introduction: Chimerism after orthotopic liver transplantation (OLT) has largely been investigated in intrahepatic cellular constituents. However, little is known about chimerism in the extrahepatic and large intrahepatic bile ducts. Our aim was to evaluate the presence and extent of chimerism after OLT in the peribiliary glands (PBG) and the luminal epithelium of the large donor bile ducts.

Successful Thrombectomy via a Surgically Reopened Umbilical Vein for Extended Portal Vein Thrombosis Caused by Portal Vein Embolization prior to Extended Liver Resection.

Selective portal vein embolization (PVE) before extended liver surgery is an accepted method to stimulate growth of the future liver remnant. Portal vein thrombosis (PVT) of the main stem and the non-targeted branches to the future liver remnant is a rare but major complication of PVE, requiring immediate revascularization. Without revascularization, curative liver surgery is not possible, resulting in a potentially life-threatening situation.

Necroptosis in Cholangiocarcinoma.

Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms.

First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion.

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation.

Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury.

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking.

Repopulating the biliary tree from the peribiliary glands.

The larger ducts of the biliary tree contain numerous tubulo-alveolar adnexal glands that are lined with biliary epithelial cells and connected to the bile duct lumen via small glandular canals. Although these peribiliary glands (PBG) were already described in the 19th century, their exact function and role in the pathophysiology and development of cholangiopathies have not become evident until recently. While secretion of serous and mucinous components into the bile was long considered as the main function of PBG, recent studies have identified PBG as an important source for biliary epithelial cell proliferation and renewal.

Liver Transplantation in Groningen, The Netherlands: A Single Center Status Report.

The liver transplantation program of the University Medical Center Groningen in the Netherlands was started in 1979, making it one of the first programs worldwide. During the past 36 years, a total of 1478 liver transplantations have been performed, 459 of which were in children. One of the first patients transplanted in 1979 is still alive and is one of the longest surviving patients after liver transplantation worldwide.