Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation

Brunner, Stefan M.; Junger, Henrik; Ruemmele, Petra; Schnitzbauer, Andreas A.; Doenecke, Axel; Kirchner, Gabriele I.; Farkas, S.; Loss, Martin; Scherer, Marcus N.; Schlitt, Hans J.; Fichtner‐Feigl, Stefan

doi:10.1016/j.jhep.2012.12.022

Cited by 90 publications

(83 citation statements)

References 32 publications

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“…Nevertheless, improved preservation and perfusion of the peribiliary vascular plexus as observed in the HMP group may result in faster and more efficient regeneration of the biliary epithelium. Two recent clinical studies have demonstrated that biliary epithelial cell loss can be found in more than 80% of all human liver grafts before transplantation [11], [22]. This interesting new finding has changed the perspective from which to view the pathogenesis of biliary strictures after transplantation as it suggests that the critical factor that determines whether a graft will develop biliary strictures or not is insufficient biliary regeneration rather than the initial biliary injury [23].…”

Section: Discussionmentioning

confidence: 99%

Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated after Circulatory Death

et al. 2014

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BackgroundLivers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model.MethodsAfter 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system.ResultsAfter reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024).ConclusionsOxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.

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Section: Discussionmentioning

confidence: 99%

Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated after Circulatory Death

et al. 2014

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“…(11) Three independent clinical studies recently demonstrated that the majority of donor livers have histological evidence of extensive biliary IRI at the time of transplantation. (12)(13)(14) In particular, the degree of biliary epithelial loss, mural necrosis, and injury of the deep peribiliary glands (PBG) and peribiliary vascular plexus (PVP) at the time of transplantation has been associated with the development of NAS after transplantation. (12)(13)(14) The PBG contain biliary stem/progenitor cells that are involved in the regeneration and repair of the bile duct epithelium after severe injury.…”

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confidence: 99%

Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers

et al. 2018

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Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; http://www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS (before DHOPE; baseline) and after graft reperfusion in the recipient. Histological severity of biliary injury was graded according to an established semiquantitative grading system. Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls. Baseline characteristics and the degree of bile duct injury at baseline (end of SCS) were similar between both groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with baseline. In contrast, in DHOPE‐preserved livers, the degree of bile duct injury did not increase after reperfusion. Moreover, there was less injury of deep PBG (P = 0.04) after reperfusion in the DHOPE group compared with controls. In conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation. Liver Transplantation 24 655–664 2018 AASLD.

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“…24,25 Severe injury to biliary epithelial cells followed by insufficient regeneration of these cells has been suggested as a potential factor in the development of biliary complications after clinical liver transplantation. 26,27 Actually, the detailed pathogenesis of this acute periductal reaction is poorly understood, 25 and therefore, it remains a matter of speculation; these insufficient regenerated biliary tracts might play a role for S4-related complications. In clinical, delayed onset for drainage requirements (median 22 days postoperatively: 7-42 days, Table 1) is one of its unique features after SLT.…”

Section: Discussionmentioning

confidence: 99%

Improving graft survival by understanding the mechanism of segment 4 complications after split liver transplantation

Komatsu

Vicentine

Mouhadi

et al. 2016

Clinical Transplantation

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Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation

Cited by 90 publications

References 32 publications

Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated after Circulatory Death

Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated after Circulatory Death

Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers

Improving graft survival by understanding the mechanism of segment 4 complications after split liver transplantation

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