Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.
[Show abstract][Hide abstract] ABSTRACT: A global rising organ shortage necessitates the use of extended criteria donors (ECD) for liver transplantation (LT). However, poor preservation and extensive ischemic injury of ECD grafts has been recognized as an important factor associated with primary non-function, early allograft dysfunction, and biliary complications after LT. In order to prevent for these ischemia-related complications, machine perfusion (MP) has gained interest as a technique to optimize preservation of grafts and to provide the opportunity to assess graft quality by screening for extensive ischemic injury. For this purpose, however, objective surrogate biomarkers are required which can be easily determined at time of graft preservation and the various techniques of MP. This review provides an overview and evaluation of biomarkers that have been investigated for the assessment of graft quality and viability testing during different types of MP. Moreover, studies regarding conventional graft preservation by static cold storage (SCS) were screened to identify biomarkers that correlated with either allograft dysfunction or biliary complications after LT and which could potentially be applied as predictive markers during MP. The pros and cons of the different biomaterials that are available for biomarker research during graft preservation are discussed, accompanied with suggestions for future research. Though many studies are currently still in the experimental setting or of low evidence level due to small cohort sizes, the biomarkers presented in this review provide a useful handle to monitor recovery of ECD grafts during clinical MP in the near future.
Journal of Hepatology 05/2014; 61(3). DOI:10.1016/j.jhep.2014.04.031 · 11.34 Impact Factor
"Serum AST and total bilirubin levels were similar between the HMP and SCS livers, indicating that HMP with a synthetic perfusate can be used successfully to preserve donor livers before transplantation. Applying this same solution and technology to human livers achieved satisfactory transplantation outcomes compared with those after SCS . The MP preservation solution Polysol was developed in 2005 and contains many vitamins and a protein-like, enriched tissue culture medium for functional recovery during preservation, which is expensive [40,41]. "
[Show abstract][Hide abstract] ABSTRACT: Donation after circulatory death (DCD) is a promising solution to the critical shortage of donor graft tissue. Maintaining organ viability after donation until transplantation is essential for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in clinical practice. However, ischemic damage present in DCD grafts jeopardizes organ viability during cold storage, and whether static cold storage is the most effective method to prevent deterioration of organ quality in the increasing numbers of organs from DCD is unknown. Here we describe the historical background of DCD liver grafts and a new preservation method for experimental and clinical transplantation. To prevent ischemia-reperfusion injury in DCD liver grafts, a hypothermic machine perfusion (HMP) technique has recently been developed and may be superior to static cold preservation. We present evidence supporting the need for improving liver perfusion performance and discuss how doing so will benefit liver transplantation recipients.
"Therefore, it can be argued that perfusates provide more accurate information about conditions predisposing to ITBL than biopsies. Previous studies have reported the successful use of perfusates to predict graft survival and graft dysfunction by measuring hyaluronate-and aminotransferases    and recent experimental studies describe the identification of perfusate markers in hypothermic machine perfusion of marginal grafts  . These markers, however, concerned hepatocyte injury and associated graft primary non-function, but failed to detect the degree of biliary injury in liver grafts. "
[Show abstract][Hide abstract] ABSTRACT: Ischemic-type biliary lesions (ITBL) are the second most common cause of graft loss after liver transplantation. Though exact pathophysiology of ITBL is unknown, bile duct injury during graft preservation is considered to be a major cause. Here, we investigated whether the release of cholangiocyte-derived microRNAs (CDmiRs) during graft preservation is predictive for the development of ITBL after liver transplantation.
Graft preservation solutions (perfusates) and paired liver biopsies collected at the end of cold ischemia were analysed by RT-qPCR for CDmiR-30e, CDmiR-222 and CDmiR-296 and hepatocyte-derived miRNAs (HDmiRs) HDmiR-122 and HDmiR-148a. MicroRNAs in perfusates were evaluated on their stability by incubation and fractionation experiments. MicroRNA profiles in perfusates from grafts that developed ITBL (n=20) and grafts without biliary strictures (n=37) were compared.
MicroRNAs in perfusates were proven to be stable and protected against degradation by interacting proteins. Ratios between HDmiRs/CDmiRs were significantly higher in perfusates obtained from grafts that developed ITBL (P<0.01) and were identified as an independent risk factor by multivariate analysis (P<0.01, HR: 6.89). The discriminative power of HDmiRs/CDmiRs in perfusates was validated by analysis of separate brain death- (DBD) and cardiac death donors (DBD; P⩽0.016) and was superior to expression in liver biopsies (C=0.77 in perfusates vs. C<0.50 in biopsies).
This study demonstrates that differential release of CDmiRs during graft preservation is predictive for the development of ITBL after liver transplantation. This provides new evidence for the link between graft-related bile duct injury and the risk for later development of ITBL.
Journal of Hepatology 08/2013; 59(6). DOI:10.1016/j.jhep.2013.07.034 · 11.34 Impact Factor
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