ex-situ-normothermic-machine-perfusion-of-donor-livers

<em>Ex Situ</em> Normothermic Machine Perfusion of Donor Livers

In contrast to conventional static cold preservation (0-4 &#176;C), ex situ machine perfusion may provide better preservation of donor livers. Continuous ...

University of Groningen, University Medical Center Groningen

The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps.

Hypothyroidism improves random-pattern skin flap survival in rats.

The origin of biliary strictures after liver transplantation: is it the amount of epithelial injury or insufficient regeneration that counts?

Livers 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.

Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death.

The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation.

Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures.

The incidence, pathogenesis and management of the most common biliary complications are summarized, with an emphasis on nonanastomotic biliary strictures (NAS) and potential strategies to prevent NAS after liver transplantation.

Biliary complications after orthotopic liver transplantation.

Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.

Article	Year
Hypothyroidism improves random-pattern skin flap survival in rats. The Journal of surgical research\| PubMed ID: 22521221	2012
The origin of biliary strictures after liver transplantation: is it the amount of epithelial injury or insufficient regeneration that counts? Journal of hepatology\| PubMed ID: 23466306	2013
Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PloS one\| PubMed ID: 24551114	2014
Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. Journal of hepatology\| PubMed ID: 24560661	2014
Biliary complications after orthotopic liver transplantation. Current opinion in organ transplantation\| PubMed ID: 24752062	2014
Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PloS one\| PubMed ID: 25369327	2014
Preservation Injury of the Distal Extrahepatic Bile Duct of Donor Livers Is Representative for Injury of the Intrahepatic Bile Ducts. Journal of hepatology\| PubMed ID: 25796482	2015

Negin Karimian

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