器官移植突破表明人类肝脏可以在体外存活数天

StephenW

器官移植突破表明人类肝脏可以在体外存活数天米歇尔·斯塔尔2022 年 6 月 1 日当供体器官可供需要移植的人使用时，医务人员需要迅速采取行动。膨胀的冰晶破坏脆弱的组织只需要几个小时，留下不到 12 小时的时间来评估、运输和植入新器官。这不仅造成了执行精细程序的巨大时间紧迫，而且使许多器官无法移植。但一项新的突破可以极大地改善肝移植的前景：科学家们将肝脏在非冷冻条件下保存了三天，然后将其移植到患者体内。此外，移植中心认为该肝脏无法生存，因为它有肿瘤并且来自需要评估和治疗的败血症（细菌感染）患者。为期三天的窗口允许研究人员执行这些操作，清除肝脏进行移植。一年后，接受者完全健康，肝功能正常，生活质量正常。尽管在广泛的临床应用之前需要进行进一步的调查，但结果可能意味着未来被认为可移植的肝脏数量会增加。“过去 30 年肝移植的成功导致全球器官短缺……可用器官的缺乏仍然是限制移植成功的最重要因素，”由外科医生 Pierre-Alain Clavien 领导的一组研究人员写道瑞士苏黎世大学医院和 Wyss Zurich 医院。“这一首次临床成功为临床研究开辟了新的视野，并有望延长长达 10 天的时间窗口，以评估供体器官的活力，并将紧急和高要求的手术转变为选择性手术。”注意：下面有器官的图形图像，所以如果您不想看到它，请不要进一步滚动。该团队用来保护肝脏的技术在医学界越来越受到关注。这叫做异位（异位）常温灌注，原理很简单。器官被放置在无菌环境中，并保持在 37 摄氏度的温度，大约是正常人体温度（“正常体温”）。在这种环境中，它不断被模拟人体功能的液体冲刷，例如营养、激素和血液。 2020 年，Wyss Zurich 展示了他们的灌注技术的功效，让人类肝脏在体外保持正常功能 7 天。人肝离体灌注灌注浴中的供体肝脏。 （Clavien 等人，自然生物技术，2022 年）2021 年 5 月 19 日，他们的研究向前迈出了一大步。他们从一名患有侵袭性腹部肿瘤和脓肿以及抗生素耐药细菌复发性败血症的 29 岁女性那里获得了肝脏移植物。肝脏本身有一个未知性质的肿瘤，在认为该器官适合移植之前需要进行诊断性检查。另一边是接受者：一名患有晚期肝硬化、严重门静脉高压症、多发性和复发性肝癌的 62 岁男子。他完全了解该程序的实验性质，并同意风险，尤其是因为他的条件如此先进，以至于他通过正常的移植名单及时接受肝移植的机会几乎为零。2021 年 5 月 22 日，在供体器官恢复后的第四天开始，进行了移植手术。这个过程很复杂，需要一组工程师、生物学家和医生一起工作。这是成功的，一个响亮的：当血液在完全没有血液供应的一段时间后返回组织时，绝对没有任何可能发生的损伤迹象，即所谓的再灌注损伤。研究人员说，结果与活体捐赠相当，即从自愿的活体捐赠者身上提取器官移植物并直接移植到接受者体内。唯一需要的干预是为期六周的基本标准免疫抑制方案，以避免受体的身体排斥供体器官。移植的肝脏功能正常，并且没有显示出不良反应——没有排斥的迹象，也没有常见的胆管损伤。一年后，他的表现仍然很好。总而言之，这是一个美妙且极有希望的结果。“由于肝移植仍然是目前最具挑战性和资源密集型的外科手术之一，目前作为一项不定期的紧急手术进行，长期的异位灌注可以使此类手术成为一种选择性手术，就像活体捐赠一样，”研究人员说。
“我们认为，第一次移植成功的异位常温灌注保存器官可以为许多肝脏疾病的治疗开辟新的视野。”
该研究已发表在《自然生物技术》上。

StephenW

Organ Transplant Breakthrough Shows Human Liver Can Survive Outside The Body For Days
MICHELLE STARR
1 JUNE 2022

When a donor organ becomes available to someone in need of a transplant, medical personnel need to act quickly. It only takes a few hours for expanding ice crystals to damage delicate tissue, leaving a window of less than 12 hours to assess, transport, and implant the new organ.

This not only creates a tremendous time crunch to perform a delicate procedure, but leaves many organs unviable for transplantation.

But a new breakthrough could vastly improve the landscape of liver transplantation: Scientists kept a liver preserved for three days, in non-frozen conditions, before transplanting it into a patient.

Moreover, that liver had been deemed unviable by transplant centers, since it had a tumor and came from a patient with sepsis (bacterial infection) that needed to be assessed and treated. The three-day window allowed the researchers to perform these actions, clearing the liver for transplant.

A year later, the recipient was perfectly healthy, with normal liver function and a normal quality of life. Although further investigation is necessary ahead of widespread clinical uptake, the results could mean, in the future, an increase in the number of livers deemed viable for transplantation.

"The success of liver transplantation over the past 30 years has led to a worldwide shortage of organs … the lack of available organs remains the single most important factor limiting the success of transplantation," writes a team of researchers led by surgeon Pierre-Alain Clavien of University Hospital Zurich and Wyss Zurich in Switzerland.

"This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure."

Note: there's a graphic image of the organ below, so don't scroll further if you don't want to see it.

The technique the team used to preserve the liver is one that has been gaining increasing traction in the medical world.

It's called ex situ (off site) normothermic perfusion, and the principle is simple. An organ is placed in a sterile environment and maintained at a temperature of 37 degrees Celsius, around normal human body temperature ("normothermic").

In this environment, it's constantly flushed with fluids mimicking human body functions, such as nutrients, hormones, and blood. In 2020, Wyss Zurich demonstrated the efficacy of their perfusion technology by keeping a human liver functioning normally for seven days outside of the body.

human liver ex vivo perfusionThe donor liver in the perfusion bath. (Clavien et al., Nature Biotechnology, 2022)

On 19 May 2021, their research took a massive step forward. They were offered a liver graft from a 29-year-old woman suffering invasive abdominal tumors and abscesses, as well as recurrent sepsis from antibiotic resistant bacteria.

The liver itself had a tumor of an unknown nature, which would have required a diagnostic work-up before the organ could be deemed suitable for transplantation.

On the other side, there was the recipient: a 62-year-old man suffering from advanced cirrhosis, severe portal hypertension, and multiple and recurrent liver cancer.

He was fully informed of the experimental nature of the procedure, and agreed to the risks, not least because his conditions were so advanced that he had a near-zero chance of receiving a liver transplant in time via the normal transplant lists.

On 22 May 2021, on the beginning of the fourth day after the donor organ was recovered, the transplant procedure took place. The procedure was a complicated one, requiring a team of engineers, biologists, and physicians all working together.

And it was a success, a resounding one: There was absolutely no sign of the damage that can occur, known as reperfusion injury, when blood returns to tissue after a period of no blood supply at all.

The result was comparable, the researchers said, to living donation, when an organ graft is extracted from a willing living donor and transplanted directly into the recipient.

The only intervention required was the basic, standard regime of immunosuppression for six weeks, to avoid the recipient's body rejecting the donor organ. The transplanted liver functioned normally, and showed no adverse effects – no signs of rejection, or injury to the bile ducts, which is common.

A year later, he was still doing well. In all, it's a wonderful and highly promising result.

"As liver transplantation remains one of the most challenging and resource-intensive surgical procedures currently performed as an urgent procedure out of regular schedule, long-term ex situ perfusion could enable such surgeries to become an elective procedure, like living donation," the researchers say.

"We think that this first transplantation success with an ex situ normothermic perfusion preserved organ can open new horizons in the treatment of many liver disorders."

The research has been published in Nature Biotechnology.

StephenW