木瓜直播

Using normothermic liver perfusion (NMP) to improve and allow objective measurement of function could save as many as seven of 10 marginal donor livers from rejection, a British study suggested.

That could boost the supply of transplantable organs, shorten wait lists, and reduce mortality, said Hynek Mergental, MD, PhD, of Queen Elizabeth Hospital in Birmingham, U.K., and colleagues.

As shown in their Viability Testing and Transplantation of Marginal Livers trial, published online in , objective criteria by lactate clearance determined liver viability in 22 of 31 organs (71%) transplanted after a median preservation time of just under 18 hours.

The 3-month survival rate was 100%, but during a median follow-up of 542 days, four patients (18%) developed biliary strictures requiring re-transplantation.

"This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischemia," the researchers wrote.

They noted that approximately one-third of donated livers are discarded in the U.K. because they don't meet desired criteria, and decisions on viability usually depend on surgeons' subjective assessments of the appearance of grafts.

The study included 31 donor livers and assessed them for viability based on lactate clearance to a level of ≤2.5 mmol/L within 4 hours. During the NMP procedure, 25 livers quickly recovered metabolic activity and were clearing lactate to the targeted level.

Among the discarded livers was one in which biopsy of a suspicious colonic lesion confirmed malignancy, even though the organ had met functional viability criteria, the researchers reported. Three other livers initially qualified but exhibited rapid deterioration of metabolic function with increasing lactate levels within the first 4 hours. In two of these cases, the livers were discarded before the transplant process had begun, while in the third, the explant was already underway.

"Whilst liver transplantation is one of the most advanced surgical procedures, up to now, there has been no objective mean to assess suitability of donor livers for transplantation," Mergental said in a press release. "The VITTAL trial validated our pre-clinical research and pilot clinical observations and these viability criteria can now guide transplant teams worldwide to provide access to the life-saving transplantation to more patients in need."

The majority (64%) of VITTAL's intended liver recipients were men, and median patient age was 56 (range of 46-65). The leading indication for transplantation was alcohol-related liver disease (36%), followed by primary sclerosing cholangitis (27%) and non-alcoholic steatohepatitis (18%). In three patients (14%), underlying liver disease was complicated by liver cancer.

Mergental and co-authors noted that despite a waiting list mortality in Western countries of 20-30%, an increasing proportion of livers go unused owing to concerns about primary non-function and early graft

"The decision to discard donor livers is still largely based upon donor history and subjective assessment by the transplanting surgeon. Standard cold static preservation does not allow for any assessment of liver function, and the only other source of information is liver histology, which is able to diagnose severe large droplet fatty change, a well-recognized risk factor for non-function," the team stated.

Asked for his perspective, Robert M. Cannon, MD, a liver transplant surgeon at the University of Alabama at Birmingham, who was not involved with the study, noted that the perfusion protocol differs substantially from usual practice in U.S. transplant centers since normothermic perfusion has not yet been widely adopted in this country.

He added that clinical trials of the two major U.S. normothermic perfusion platforms, however, are underway or nearing completion in the U.S. pursuant to obtaining FDA approval for routine clinical use; Cannon is a principal investigator for

"Normothermic perfusion is a novel step, and we expect that FDA approval of normothermic perfusion will lead to more widespread adoption of the platform," he told 木瓜直播. "Once we're able to widely implement normothermic perfusion in liver transplantation, I think the findings of the Birmingham, U.K., group will definitely be significant for U.S. practice and will lead to a marked expansion of the donor pool to include livers that we once thought were too risky for transplantation."

Moving from subjective to objective assessment of organ viability is a crucial step, Cannon continued. "At present we're left to using our best guess based on clinical experience and limited available data to determine if a given organ is suitable for transplant. The consequences of making the wrong decision and transplanting a liver that does not work can be disastrous for the patient, so having the ability to objectively assess a donor liver's function prior to implanting it in a patient will be, in my opinion, a revolution in liver transplant that will lead to significantly greater access to liver transplantation for those in need."

Comment