In the midst of a revolution in liver transplantation

Młody mężczyzna w białej koszuli stoi w sali szpitalnej
Today at the Medical University of Warsaw (WUM), we can still check before transplantation whether an organ will take up its function. We perform split liver transplants. We transplant livers to oncological patients, such as those with metastatic colorectal cancer. Michał Grąt, MD, PhD, head of the Department of General, Transplantation and Liver Surgery UCC WUM, talks about state-of-the-art methods that can save more and more patients.

As of 2022, 134 liver transplants have been performed in the clinic you run. Last year—258—that's almost twice as many patients saved. What changed that made such progress possible? 

I took over the clinic in September 2022. When you compare the statistics since then with previous years—you will find that we have increased the number of transplants performed by almost three times. So what has changed? Primarily, we have very intensively implemented liver perfusion methods into clinical practice. As a result, we are able to use grafts, i.e. organs taken from donors that are not optimal and whose transplantation is associated with increased perioperative risk. Perfusion methods reduce this risk. 

Yet another issue: split livers. The number of split liver transplants performed in our clinic is not very large, but already significant. Last year we transplanted seven divided livers, that is, 14 transplants were successfully performed from seven available organs.

International cooperation is also an important aspect. Last year we started using organs donated outside Poland—in Germany, Austria, Bulgaria, Lithuania. It is important to arrange transport to our center in such a way that the time of organ ischemia is not prolonged to unacceptable levels.

In conclusion, the key, when it comes to increasing the number of transplants, is to strive to use every organ that can be transplanted with acceptable risk. This policy has led to the fact that we can perform more and more transplants and qualify more and more patients for this procedure.

Has the number of organ donors also increased in recent years?

The number of identified deceased donors is increasing, and this is a good trend. However, the increase is insignificant. Interestingly, it is known that the number of deceased from whom organs could be taken is the same in many countries. And yet in Poland we have twice as many identified deceased donors as in Spain, for example. Therefore, we should strive to ensure that every dead person is evaluated as a potential organ donor—because this allows us to save the lives of others.

What could be the reason that we have fewer donors identified in Poland?

There are many reasons for this. Certainly, for this to change, there needs to be broad public acceptance of transplantation. It is necessary to talk about transplantation. And not only in medical circles, but precisely outside them. It is worthwhile for this topic to appear in family conversations, in discussions between friends. In Polish law there is a rule that if the deceased during their lifetime did not object to organ donation, we can get them. On the other hand, of course, before doing so, doctors talk to families, and these conversations are sometimes very difficult. If we manage to tame the idea of transplantation, then the family of the deceased will have fewer doubts about the removal of his organs.

Can the liver be harvested only from a deceased organ donor, or is it also possible from a living one?

It is also possible to harvest a living organ donor. Such procedures are carried out as part of a program that Marek Krawczyk, MD, PhD, of the Children's Health Center, has started with Piotr Kalicinski, MD, PhD. Liver fragments are taken from living people, usually family members, and transplanted into children. This method has improved the very poor situation of pediatric patients in need of transplantation and reduced the mortality rate of children due to liver disease. Previously, the organ pool for pediatric patients was limited, by the fact that donations from deceased children are very rare. I have no doubt that transplantation of liver fragments from living donors for adult recipients also has a place in transplantology. We are moving towards this at our clinic. We have already managed to gather the appropriate equipment. We are preparing quietly, because the most important thing in this case is the safety of the organ donor. There have already been four such transplants in the history of our clinic. Now it's time to return to it. I think that this year we will already start performing such operations.

In transplantology, it is not only the procurement and transplantation itself that is important, but also the storage of the harvested organ. You mentioned modern perfusion techniques. What do they consist of?

These techniques are perfusion of the liver in hypothermia with oxygenation and perfusion in normothermia. Perfusion in hypothermia is carried out at a low temperature—about 12 degrees C. In doing so, a small amount of oxygen is supplied to the liver. This is to prepare the transplanted organ for subsequent reperfusion. Reperfusion occurs when the liver is already in the body of the recipient and blood flow is restored there. Then a number of mechanisms occur at the cellular level that cause the liver to be more or less damaged by the body of the recipient. This always happens after transplantation, the idea is to minimize this damage. And perfusion in hypothermia allows this.
On the other hand, with perfusion in normothermia, we are able to assess whether the organ donor liver is functioning after blood flow is restored. Here we use a special preparation, which is prepared on the basis of red blood cell concentrate. Using such "artificial blood" we recreate its flow through the organ even before transplantation. We can then perform biochemical tests, observe whether the liver secretes bile, etc. Based on this, we decide whether the organ is safe to use. We use this technique when the organ donor shows signs of liver failure. The key question is whether we are dealing with transient failure associated with death or irreversible failure. In the former case, adverse processes can be reversed fairly quickly. In the second situation—the organ cannot be used. 

It is worth recalling that once, for many years, liver transplantation was based on storing the organ in perfusion fluid at a low temperature—about 4 degrees C.
Now, using modern methods, we are able not only to store the organ, but also to prepare it for ischemia-reperfusion damage. By doing so, we improve the results of transplantation. We use organs initially with an increased risk, but then this risk is lowered and the final risk is similar to when we have optimal organs. 

Are these modern perfusion methods used routinely in your clinic?

Yes, in justified cases, that is, when we have an organ with increased risk. In contrast, optimal livers, of which there are a minority, do not require the use of modern perfusion methods. Most scientific data indicate that the use of these techniques in this case does not improve the clinical outcome of transplantation. If we were limited to using only optimal livers, most patients would unfortunately not live to see surgery. 

What patients are most often qualified for liver transplantation?  

Most often, these are patients with end-stage cirrhotic liver failure. Cirrhosis can be caused by various factors: infection with hepatotropic viruses, alcohol abuse, the course of autoimmune diseases. The chronically damaged liver works worse and worse, until finally we reach the point when significant portal hypertension develops, which in itself can be the cause of the patient's death. Progressive organ failure also leads to death. The only salvation then is to replace the diseased liver with a functioning one that will not cause portal hypertension.

Liver transplantation can also be a lifesaver for oncology patients. They constitute a growing group among our patients. Recent years have brought a revolution in oncology transplantation. It is worth noting here that the liver is a rather immunologically privileged organ. After transplantation, immunosuppression here is significantly less than in heart or kidney transplantation. We used to think of liver transplantation only in the context of hepatocellular carcinoma, metastatic neuroendocrine tumors and some other rare cancers. Today, we have expanded these indications. We qualify patients with cancers of the intrahepatic and extrahepatic bile ducts. We also perform transplant procedures on patients with metastases of colorectal cancer—one of the more common cancers—to the liver. And this is a huge patient population. Of course, not everyone who has unresectable liver metastases will have a transplant. But we are able to select a group from among them that can benefit enormously from transplantation. With transplantation, we are able to increase the survival period of such patients to more than five years. Which is a very big achievement in the face of the alternative they have—palliative treatment and a few or several months of life.

It is said about your clinic that it performs borderline transplants, that is, you deal with very difficult cases. Is this true?

Yes, this is true. We try to qualify for transplantation any patient for whom we are able to provide at least a 50 percent chance of surviving liver transplantation. Consequently, we have a great number of patients who have a huge risk of liver transplantation—a 50 percent risk of perioperative death. At the same time, however, these are patients who have a 100 percent risk of death without transplantation. So we turn a 100 percent certainty of death into a 50 percent chance of life. We perform surgeries on the sickest patients, such as those with extensive portal vein thrombosis, severe hepatopulmonary syndrome, even on critically ill patients, as long as we can establish that transplantation offers an acceptable chance of survival. We are not afraid to take risks to save at least some of these most seriously ill patients.

What is the prognosis after liver transplantation—what percentage of patients survive?

The results of liver transplantation depend on which patients undergo surgery. As I mentioned, for the most severe patients, the risk of death can reach 50 percent. But there are some patients in whom the risk does not exceed 5 percent. It is assumed that on average in the peri-transplantation period the mortality rate is 10 percent. This means that 1 in 10 patients will not survive the liver transplantation. This is influenced by various factors related to the organ donor, with the recipient and the procedure itself.   
If we consider the entire population of recipients (and very severe patients and those in better condition)—then 5 years after transplantation 70 percent survive, and 10 years after transplantation—60 percent. About 50 percent 20-year survival is also observed.

How is a liver transplant performed and how long does such a procedure take?

It is always performed through a laparotomy, which is a wide opening of the abdominal layers. The procedure usually takes 5 to 8 hours, but it can also take 12 or 13. It depends on many factors, on the anatomy, on previous surgical treatment, on the severity of the liver disease. We have adopted the rule that one team performs a hepatectomy, that is, removes the diseased liver, and another team implants the organ. There 
are also procedures where we collaborate with cardiac surgeons, a clinic led by Mariusz Kusmierczyk, MD, PhD. Recently, we performed a transplantation using extracorporeal circulation, or ECMO, in a patient in very serious condition. Without the help of cardiac surgeons, such a patient would have had no chance of both surviving the liver transplant and the perioperative period. 

Last year you performed the first transplantation of one divided liver to two recipients in Poland. What do we gain from such a procedure, and does it involve additional risks?

The biggest gain is that we save not one but two patients from death. Recipients of such divided livers are patients (usually women) whose body weight is 40-50 kilograms. But not only that. We can calculate what the ratio of liver weight to body weight should be in a particular recipient. Ratios are used for this purpose, thanks to which we draw safe boundaries and know how large a liver fragment a specific recipient should get. 
Interestingly, there are already articles in the transplant literature whose authors pose the question: aren't liver transplant teams ethically obligated to share every organ that can be shared. If the pool of organs is limited, all our efforts should aim to perform as many transplants as possible, because this is an opportunity for as many patients as possible. 
Of course, split liver transplants are associated with an increased risk of complications. The liver is not whole, it has fewer hepatocytes, and we also have the additional procedure of dividing it. These are very difficult operations. But most importantly, they are an opportunity for those patients who otherwise would not live to see transplantation at all.
It is worth mentioning that we use the experience of transplanting divided livers in transplanting whole organs. We know that when transplanting only fragments, we have to use different kinds of portal flow modulation techniques. This is what is done in liver transplantation from a living organ donor. We took advantage of this knowledge and were among the first in the world to implement portal flow modulation (blood flow through the vessels in the liver) in whole liver transplantation. Thanks to this, we were able to reduce the risk of a complication several times, which is clotting of the hepatic artery. And this is a fairly common and severe complication, requiring retransplantation or leading to death.

The high number of successful transplants and the innovation of the procedures have determined that your clinic has become one of the largest liver transplant centers in the world. What does this entail?

First of all, the fact that we are identified by patients. The more widely the clinic is talked about, the more people in Poland will know about it. We want to reach as many patients as possible. People suffering from end-stage liver disease or liver cancer are looking for consultation, and we want them to come to us so we can assess whether we can save them. The role of a large center like ours is to provide consultation for the entire country.

And does the clinic cooperate with any European transplant centers?

In 2022, we started a very intensive scientific exchange with Medical School Hannover. It is one of the most recognized transplant centers in Europe. It was created by Rudolf Pichlmayr, MD, PhD, and is currently headed by Moritz Schmelzle, MD, PhD, who recently visited WUM and gave a lecture to our PhD students.  A large part of our clinic's team visited the center in Hannover. This gave us a unique opportunity to take a new look at some aspects of liver transplantation. As a result, we introduced a number of solutions that allowed us to save some of the sickest patients that we would not have saved before. This includes, for example, methods that make it possible to keep a patient without a liver for one-two days. We had such a patient in the clinic. He wouldn't live to see the transplant because his liver was severely poisoning his body. So we removed the liver and the patient survived a certain period without it—as part of his treatment in the intensive care unit. 
Of course, such cases are not a success story. I emphasize, we are dealing with the most seriously ill patients, of whom a minority manage to save. However, without this procedure, they would have all died. 

What are the biggest challenges today when it comes to liver transplants?

The biggest challenge now seems to be the introduction of a live organ donor transplantation program in Poland. We are pushing hard for this. We would also like to have all the techniques used in the world related to liver transplantation available in our country. We are also moving towards this at our clinic. These include, for example, experimental methods of transplanting liver fragments from deceased donors or two-stage transplantation methods for oncology patients. There are also methods of liver autotransplantation in the world for patients with unresectable tumors or parasitic infection. In this case, the patient's liver is taken out, operated on outside the body and implanted back in. Introducing these experimental methods in Poland will allow us to save even more patients.

Interviewed by Iwona Kołakowska
Fot. Michał Teperek
Communication and Promotion Office