NEJM: An important breakthrough in liver transplantation!

Speaking of organ transplantation, what do you think of first? The last weapon for doctors and patients in the face of organ failure? Save the lives of tens of thousands of people in the relay race every year? Or is it one after another touching story of donation? But Singularity's thoughts are a bit heavy: Every year, there are about 300,000 patients waiting for transplantation in my country, but only more than 10,000 people have the opportunity to wait for a suitable donor organ and undergo surgery.

And how to "preserve freshness" of organs from donation to maintenance, from transportation to transplantation, this process of "traveling through mountains and rivers"? Recently, the liver transplant team from the University of Groningen in the Netherlands published the latest research data in the New England Journal of Medicine.
It shows that compared with conventional static cryopreservation, hypothermic oxygenation mechanical perfusion (HOPE) preservation of the liver will be quite effective.
A new way of feasibility.

Research data shows that the circulating dead donor (DCD) liver preserved by the HOPE method has a relative reduction of 68% in the risk of non-anastomotic biliary stricture (NABS) after liver transplantation, and the risk of complications after a variety of liver transplants It also dropped significantly.

The dangerous NABS and the reduced risk of multiple complications are of course good news for improving the prognosis of patients.
It also points out a new direction of exploration for ensuring the quality of transplanted livers and improving the utilization rate of donor livers [1].

The difference between 6% and 18% is clear at a glance (picture source: NEJM) At present, in my country, citizens donate organs after death, especially circulating dead donors becoming the main force in organ transplantation.

However, circulating dead donors have longer warm ischemia than brain dead donors (DBD), and their organs are more severely damaged, and the prognosis of transplantation is often unsatisfactory.

Taking liver transplantation as an example, the risk of NABS after circulating donors is three times that of brain-dead donors [2-3].

Don't underestimate the risk of non-anastomotic biliary stenosis.
Even the transplant doctor who overcomes difficulties in the ordinary day will feel a headache and troublesome when encountering it.Because once NABS occurs, it usually causes cholestasis and cholangitis.
In severe cases, bile duct resection or even retransplantation is required.

It would be great if the cause of NABS could be eliminated in advance.

A key cause of NABS is ischemia-reperfusion injury (IRI).

So how did IRI happen? When the liver under hypoxia is exposed to oxygen again, the reactive oxygen species (ROS) in the cells are immediately released from the mitochondrial respiratory chain, which triggers downstream inflammatory responses, such as the activation of Kuffer cells and neutrophils and inflammatory factors The release of serotonin, which in turn aggravates liver damage [4].

However, when oxygen is introduced into the ischemic liver under low temperature, the rate of ROS formation slows down, while the mitochondrial oxygen reserve function gradually recovers, and the oxidative stress response will be significantly reduced when the blood flow is subsequently supplied.

In addition, HOPE can also remove succinate, the driving factor of IRI, and further reduce ischemia-reperfusion injury [4].

HOPE improves the IRI mechanism (picture source: Reference 4).
However, previous findings are mainly based on small single-center cohort studies.
So how does HOPE perform in prospective, randomized controlled studies? To this end, the Robert J.
Porte liver transplant team initiated a prospective, multi-center, randomized controlled study-the DHOPE-DCD trial [1].

During the period from January 2016 to July 2019, the researchers evaluated 245 patients and excluded donors below 40 kg, HIV, HBV, HCV positive donors, and recipients undergoing liver transplantation due to severe liver failure.
160 patients were randomized, and finally 78 people received circulatory dead donor livers by low-temperature oxygenation mechanical perfusion or conventional static cryopreservation (SCS).

The conditions of the donors and recipients of low-temperature oxygenation mechanical perfusion and regular static cryopreservation are basically the same.
The static cold ischemia time of the former is slightly shorter than that of the latter (6 hours and 11 minutes vs.
6 hours and 49 minutes), and the total storage time is longer (8 Hours 44 minutes vs.
6 hours 49 minutes). To analyze the impact of HOPE on biliary complications after DCD liver transplantation, the researchers listed the incidence of symptomatic NABS within 6 months after surgery as the main research index.
The data showed that compared with SCS, HOPE can make DCD liver The risk of NABS within 6 months after transplantation was relatively reduced by 68% (HR=0.
32).

The risk of NABS after DCD liver transplantation in the HOPE group was significantly lower.
In addition, the study also analyzed post-reperfusion syndrome, early graft dysfunction, and the cumulative number of treatments for NABS.
The HOPE group also showed a reduction in the incidence of these complications.
good.

Unfortunately, the HOPE group in this study did not show obvious advantages in terms of renal replacement therapy, ICU and hospitalization days, as well as the 1-year survival rate of transplants and patients.

HOPE vs SCS has to say that as a new type of mechanical perfusion preservation technology, HOPE's performance is really impressive.

But in fact, the history of the development of mechanical perfusion (MP) can be traced back to the 1960s, when Folkert O.
Belzer of the University of California, San Francisco developed the first hypothermic perfusion device and published a paper on NEJM.
Cases of successful kidney transplantation [5].

In 2018, David Nasralla of the University of Oxford and others reported in Nature a randomized trial of 220 liver transplant patients.
The study found that compared with SCS, normal temperature mechanical perfusion (NMP) reduced the rejection rate of donor livers by about 50%.
In the aspect of liver preservation, a beautiful answer was given [6].

However, the research team emphasized in the paper that although NMP pearls are the first, the advantage of HOPE lies in safety and flexibility, because the organ is always in a low temperature state, even if it is mishandled, it will not cause warm ischemia damage and organ loss [1].

NEJM associate editor Winfred W.
Williams and Harvard Medical School expert James F.
Markmann also said that HOPE will bring exciting new applications in the future, such as in vitro degreasing of steatosis liver, inducing liver regeneration in vitro, and gene editing methods.
Modify organs to improve the prognosis of transplantation and so on [7]. The continuous efforts of scientists in the field of HOPE preservation model transplantation are all for a simple wish-to allow more and more patients waiting for transplantation to undergo surgery as soon as possible, and to better embrace the new life.

Finally, I said, everyone should take good care of their body~ Singularity recruits everyone! Everybody Hi~! We need fresh blood to inject new energy into the singularity.

Come on, become the singularity cake and do a new job with us! These are the little friends we are currently looking for~ If you want to create and innovate with the singularity cakes, come join us.

Please send your resume and work (if any) to: hr@geekheal.
com or you can directly add to the WeChat (geekheal-xintan) of Geekheal-xintan for communication.
When adding friends, please note: recruitment + position + professional field.

We are waiting for you at Singularity.

 References: [1] van Rijn R, Schurink IJ, de Vries Y, et al.
Hypothermic Machine Perfusion in Liver Transplantation-A Randomized Trial.
N Engl J Med.
2021;384(15):1391-1401.
doi:10.
1056 /NEJMoa2031532.
[2] O'Neill S, Roebuck A, Khoo E, Wigmore SJ, Harrison EM.
A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation.
Transpl Int.
2014;27 (11):1159-1174.
doi:10.
1111/tri.
12403.
[3] Foley DP, Fernandez LA, Leverson G, et al.
Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long -term outcomes from a single center.
Ann Surg.
2011;253(4):817-825.
doi:10.
1097/SLA.
0b013e3182104784.
[4] Czigany Z, Lurje I, Schmelzle M, et al.
Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications.
J Clin Med.
2020;9(3):846.
Published 2020 Mar 20.
doi:10.
3390/jcm9030846.
[5] Belzer FO, Ashby BS, Gulyassy PF, Powell M.
Successful seventeen-hour preservation and transplantation of human-cadaver kidney.
N Engl J Med.
1968;278(11):608-610.
doi:10.
1056/NEJM196803142781108.
[6] Nasralla D, Coussios CC, Mergental H, et al.
A randomized trial of normothermic preservation in liver transplantation.
Nature.
2018;557(7703):50-56.
doi:10.
1038/s41586-018-0047-9.
[7] https ://www.
medpagetoday.
com/gastroenterology/livertransplantation/91345.
Source of head picture: KHN.
org Author of this articleDavina editor in charge | Tan Shuo3390/jcm9030846.
[5] Belzer FO, Ashby BS, Gulyassy PF, Powell M.
Successful seventeen-hour preservation and transplantation of human-cadaver kidney.
N Engl J Med.
1968;278(11):608-610.
doi: 10.
1056/NEJM196803142781108.
[6] Nasralla D, Coussios CC, Mergental H, et al.
A randomized trial of normothermic preservation in liver transplantation.
Nature.
2018;557(7703):50-56.
doi:10.
1038/s41586-018- 0047-9.
[7] Head image source: KHN.
org Author of this articleDavina Chief Editor | Tan Shuo3390/jcm9030846.
[5] Belzer FO, Ashby BS, Gulyassy PF, Powell M.
Successful seventeen-hour preservation and transplantation of human-cadaver kidney.
N Engl J Med.
1968;278(11):608-610.
doi: 10.
1056/NEJM196803142781108.
[6] Nasralla D, Coussios CC, Mergental H, et al.
A randomized trial of normothermic preservation in liver transplantation.
Nature.
2018;557(7703):50-56.
doi:10.
1038/s41586-018- 0047-9.
[7] Head image source: KHN.
org Author of this articleDavina Chief Editor | Tan Shuo2018;557(7703):50-56.
doi:10.
1038/s41586-018-0047-9.
[7] Head image source: KHN.
org AuthorDavina Responsible Editor | Tan Shuo2018;557(7703):50-56.
doi:10.
1038/s41586-018-0047-9.
[7] Head image source: KHN.
org AuthorDavina Responsible Editor | Tan Shuo