Bile Duct Damage after Cold Storage of Deceased Donor Livers Predicts Biliary Complications after Liver Transplantation

Brunner, SM; Junger, Henrik; Ruemmele, Petra; Schnitzbauer, AA; Doenecke, Axel; Farkas, S.; Loss, Martin; Scherer, MN; Schlitt, Hans J.; Fichtner‐Feigl, Stefan

doi:10.1097/00007890-201211271-00561

Cited by 16 publications

(22 citation statements)

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“…Recently, 3 independent clinical studies have demonstrated that major mucosal cell loss (>50% biliary epithelial injury) and mural stroma necrosis (<50% necrotic cells) of the large bile duct is present in more than 80% of human donor livers (both DBD and DCD) at the end of SCS and subsequent reperfusion. 4,24,27 Although biliary preservation injury is apparently almost universally present, only a minority ) concentration and pH detected in bile. Biliary bicarbonate concentrations were significantly higher in livers that had been preserved by end-ischemic HMP, COR, or SNMP compared to livers that underwent only SCS (*P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Westerkamp

Mahboub²,

Meyer

et al. 2015

Liver Transpl

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A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation. Liver Transpl 21:1300-1311, 2015. V C 2015 AASLD.Received March 17, 2015; accepted June 8, 2015.Ischemic cholangiopathy, also known as nonanastomotic biliary strictures (NAS), is one of the most prevalent and troublesome complications after liver transplantation. During NAS formation, in particular, the large (extrahepatic) bile ducts become fibrotic and/or necrotic. Patients with NAS may suffer from recurrent jaundice and episodes of cholangitis, and retransplantation may be the only curative treatment. 1 The combination of ischemia and ischemia/ reperfusion (I/R) injury has been shown to be a major Additional supporting information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Westerkamp

Mahboub²,

Meyer

et al. 2015

Liver Transpl

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“…It should be noted that endothelial preservation is difficult during prolonged preservation times (84). In biliary epithelium, ATP depletion during SCS results in detachment of cholangiocytes from the basal membrane (85). This type of injury is a feared complication after liver transplantation and, together with stromal necrosis, may lead to the formation of posttransplant biliary strictures (88).…”

Section: Clinical Status Quo Of Organ Cooling In Liver Surgery Liver mentioning

confidence: 99%

“…SCS appears to sensitize endothelial cells to reperfusion injury, since most cells die shortly after reperfusion by mechanisms that are still poorly understood (80), but could include injury induced by activated KCs (81) or induction of apoptosis by adherent platelets (82,83). The lack of perfusion during SCS results in collapse of the endothelial glycocalyx (84,85), which promotes I/R injury by facilitating endothelial activation and leukocyte adherence (86). Maintaining microvascular perfusion (see below) during preservation therefore might reduce endothelial cell injury, provided that low (portal)…”

Section: Liver Transplantationmentioning

confidence: 99%

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Olthof

Reiniers

Dirkes

et al. 2015

Mol Med

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Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided.

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“…The bile duct system and the common bile duct remain the Achilles heel of transplantation, because they are most sensitive to early ischemic injury already during cold storage. We developed a histological bile duct risk score that predicts biliary complications and may help decision making in LTx (Brunner et al 2013). …”

Section: Liver Transplantation-techniquesmentioning

confidence: 99%

Overview of the Indications and Contraindications for Liver Transplantation

Farkas

Hackl

Schlitt

2014

Cold Spring Harbor Perspectives in Medicine

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Liver transplantation is the only definitive treatment option for patients with irrevocable acute or chronic liver failure. In the last four decades, liver transplantation has developed from an experimental approach with a very high mortality to an almost routine procedure with good short-and long-term survival rates. Here, we present an up-to-date overview of the indications and contraindications for liver transplantation. It is shown how the evaluation of a candidate and finally listing for transplantation has to be performed in a multidisciplinary setting. Meticulous listing, timing, and organ allocation are the crucial factors to achieve an optimal outcome for the individual patient on the one hand, and reasonably using the limited deceased donor pool on the other hand. Living-donor liver transplantation is demanding but necessarily increasing. Because patients after liver transplantation need lifelong aftercare, it is important for primary care clinicians to understand the basic medical problems and risks.

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Bile Duct Damage after Cold Storage of Deceased Donor Livers Predicts Biliary Complications after Liver Transplantation

Cited by 16 publications

References 0 publications

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Overview of the Indications and Contraindications for Liver Transplantation

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