Liver transplants from one to a thousand: 13 was the first in the world due to trauma and not a disease

• Investigation They manage to 'resuscitate' dead organs to buy time for transplants

• Advances Closer to achieving 'universal' organs for transplantation

• Health Transplants: this is how the liver that saved Juan Antonio's life was rescued

Guadalupe González, 82 years old.

Cheerful and optimistic.

"I'm great, but I'm deaf," she confesses.

Next to her, José Julio Bautista, 61 years old.

Spontaneous and persevering.

She introduces herself: "I am José Julio Bautista and I am transplant number 1,000."

They may have many other things in common, but the main one is that

, albeit almost 35 years apart.

The Puerta de Hierro Hospital in Madrid brought them together - the

- along with the specialists who intervened and followed the process on the occasion of the Week of Liver Diseases in Madrid, which the Spanish Association for the Study of the Liver (AEEH) has organized approximately every month in an autonomous community for just over a year.

EL MUNDO had the opportunity to attend that talk of more than two hours between these patients and their doctors where they talked about their cases, very special for various reasons, and the enormous evolution of liver transplantation in those three and a half decades that separate their cases.

Guadalupe's case is special for several reasons, although she remembers the after because she did not find out about the transplant.

A bus collided with the car she was driving, causing it to crash into the center wall of a tunnel.

Although she was initially taken to the Clínico, her closest hospital, she ended up being transferred to Puerta de Hierro for a transplant.

At that time, Encarna Sánchez and José María García made an appeal on their radio programs for people to come to donate blood.

"The queue went around the building. We still had little experience, we had 12 transplants, and the case was complex. An excellent donor appeared, 30-something years old, from the north of Spain, and when we entered the operating room that was...

, there was no liver. That transplant lasted 17 hours," recalls Víctor Turrión, head of the Hospital's Surgery Service at the time and professor at the Autonomous University of Madrid, currently retired.

Guadalupe and José Julio together with the health teams that intervened in their operations in an experimental surgery operating room in the Madrid center.

Turrión relates that Guadalupe's case was historic because

.

"From this indication in Europe, 73 people have received transplants up to the year 2015, according to the European registry, it is an infrequent indication," says Valentín Cuervas-Mons, professor of Medicine at the Autonomous University and, until he retired on the 1st of September, head of the Internal Medicine Service and head of the Puerta de Hierro Liver Transplant Unit.

It is not the only historical case.

Despite having little experience and a lot of job instability at the beginning, they point out,

.

"The patient was a 12-year-old boy with ischemic heart disease due to familial hypercholesterolemia that produced atheromatous plaques and affected all the organs. The heart was transplanted first and the liver 15 days later," says Turrión.

The Puerta de Hierro Liver Transplant Unit was the second created in Spain (after the Hospital de Bellvitge, in 1984) and the first in the Community of Madrid.

A pioneer unit

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In Spain there are a total of 26

liver transplant

They are the reference hospitals in the management of liver disease.

The first unit in Spain was created at the Bellvitge Hospital in 1984 (the first liver transplant was performed on February 23 in a patient with a tumor with a complicated prognosis).

.

The Community of Madrid currently has four units (those of the

hospitals ), as well as one for children (

).

Guadalupe was number 13, on November 18, 1987, although she did not find out until days later.

"When I woke up I was scared because I didn't know what I was doing there or what had happened. A close friend was going to see me and I told her 'there I have the clothes, take them and we'll go, and we say we're going to the bank for money or to the hairdresser's because all my hair is stained.'

what had happened and that I had had a transplant, and from then on I made up my mind to be the best patient in the hospital." recounts.

"I eat once a week and I have an aperitif every day with my friends, I think it is my most important medicine because I have a slightly sad husband," Guadalupe says with a laugh and the doctors emphasize that she is a very positive person, but Also very lucky.

"The reality is that

," she adds.

"Four or five years ago Guadalupe had a complication, a narrowing of the bile duct, but it coincided that we had an American doctor visit the hospital who was an expert in a type of technology to see inside the common bile duct [coledochus] and helped us solve it," explains José Luis Calleja, current head of the hospital's Digestive Service and president of the AEEH.

Doctor Calleja recounts the no less special case of José Julio: "He was a patient who had a mixed liver disease due to alcohol and obesity/diabetes, which had caused cirrhosis. On that cirrhosis, he revealed the presence of a liver tumor (hepatocellular carcinoma

, which was initially treated with radiotherapy and when a new lesion appeared, a liver transplant was considered. In the study for the transplant, a small tumor was detected in the lung. There were doubts as to whether it was metastasis, but in the end it was a neuroendocrine tumor that was not it had nothing to do with the liver. It is a tumor with an excellent prognosis when it is small and is removed, as was the case, and that is why he underwent a transplant some time later."

José Julio perfectly remembers both interventions.

"I had surgery for lung cancer the same day as the storm Filomena, I entered at 12 in the morning with 20 centimeters of snow. And the day of the transplant, when they called me at 3 in the afternoon, I was eating in a restaurant because I Then I went to see the bullfights, my wife had bought the tickets 15 days before. Without drinking coffee I told her 'let's go, instead of bullfighting there's a good bullfight.' It was September 25, the day I was born again

" .

He had a very good postoperative period, the doctors comment, and this has a lot to do with the fact that he lost weight and the general state he was in after the transplant.

"When I was diagnosed with fatty liver five years ago,

. For the transplant I had already lost 20, I weighed 105, and now I weigh 90. After the transplant I was exhausted for 10 days, I didn't want to talk to anyone. I was I got into myself reacting because

. But then I cheered up, they discharged me and I have been coming almost every week for review, "says José Julio.

In addition, he has returned to his work activity.

"

Calleja emphasizes: "If it becomes a malignant lung tumor, it would have been impossible to transplant him because the risk of it coming back is very great, which is why he is a peculiar patient, both are."

"

", emphasizes Cuervas-Mons.

And it is that

, both in the profile of donors and recipients, as well as in the indications or the technologies used, as well as the data.

File photo of the center.

For starters, the numbers.

Liver disease is the second most common reason for lost working life years in Europe (behind ischemic heart disease), according to a study by the European Society for the Study of the Liver (EASL) and The Lancet

.

"Liver disease is increasing because it is closely linked to the incidence of obesity and diabetes.

.

In Spain, approximately 1.2% of the population were infected, a very significant number in a context of 40-odd million people.

Now it has become a residual cause, but the metabolic cause is rising in relation to fatty liver and diabetes.

In Spain, approximately

.

, which is a stable and important cause," explains Calleja.

National Liver Disease Plan

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SUPPORT: National Liver Disease Plan

Alcohol remains a very important cause of liver disease.

"From the scientific society and other societies, work is being done to create a

because it is a

, when it is already very advanced, and we need to detect patients early since most are preventable," says Calleja.

Some of the measures in that plan would be

we have liver disease,

.

"In Spain, a liter of wine is cheaper than a liter of water. There is a very clear relationship between the rate of liver disease due to alcohol and the price of alcohol in each country. In addition, in Spain a much more restrictive policy of its sale to minors under 18 years of age.

Another known reason is

.

"Ultra-processed, junk food is much cheaper than healthy food mainly due to taxes, and it also affects the poorest social classes, in such a way that what we are promoting is

. Somehow In this way they have to consider tax promotion of healthy food so that it is easier for a person to eat a salad than a hamburger with three layers of meat", continues Calleja.

In addition, the specialist indicates that there are now easier and less invasive methods in primary medicine that make it possible

.

"Analytical or elastography methods that detect the patient who is beginning to have liver disease and of course does not have any symptoms. Primary strategies to detect a fatty liver in an ultrasound, see an alteration in transaminases in the analyzes, some metabolic data in diabetic patients to do a liver check-up... In these patients, action can be taken to prevent them from developing cirrhosis".

The specialist assures that the frequency of advanced liver disease is much higher and only a minority end up having a transplant.

"For example, in patients with liver cancer, which is a growing pathology on the transplant list, only 15% are transplanted. Sometimes because the tumor is very large or metastasized, etc. On the other hand, approximately

".

On the other hand, survival after transplantation has been increasing and today is over 90% at one year and 80% at five years.

"Afterwards, approximately 2% die each year, but due to age or other pathologies unrelated to the transplant, from the same causes as the general population," says Cuervas-Mons.

On the other hand,

has promoted advanced liver surgery that is currently being performed and has been a driver of development, says Manuel Jiménez, head of the Hepatobiliopancreatic Unit and surgical manager of liver transplantation at the hospital.

"Not only has it been a car that has driven the development of liver surgery, which in some cases is called extreme surgery, but it has helped to develop many other aspects. It has changed complete

... Not only the plastic transplant, all the transplants have pulled the global development of the hospital", assures Turrión.

The surgical technique has changed radically.

"Not only the improvement of the technique and the suture or the measurement of flows that we do now, but

, it relieves the surgeon of a lot of suffering," emphasizes José Luis Lucena, head of the General Surgery section.

After all, anesthetists are in charge of the prior assessment, they are in the intraoperative period and are responsible for the postoperative period and the care that patients receive while they are in the ICU.

And technologies such as

(to contain bleeding, since the liver is a viscera that bleeds a lot).

Today, this makes it possible to reduce the complexity of the transplant, to the point that sometimes some are performed with zero perfusion (without transfusing blood).

All this has also made it possible

: "In the past it took an average of 10-12 hours. Today a transplant that goes by 6-7 hours means that there is a problem or it is a re-transplant or there has been some type of incident that has made it more complex", comments Turrión.

Indications

In the indications there has also been some evolution.

Three decades ago there were few donors and many patients, "any patient with cirrhotic, decompensated liver disease or with tumor disease was a candidate for transplantation, and the most serious patients had to be selected but who had a chance of surviving, with which the majority were much

", comments Cuervas-Mons and adds Calleja: "There are still fewer livers than patients and a selection still has to be made. Unfortunately a percentage of patients die without being able to offer a liver or because the right time has not arrived or because the patient has other diseases, other ages that prevent him from safely entering a transplant program".

Until 2015, transplants were mainly due to

.

"The liver is a rare commodity and there is a time when the patient is in such a bad condition that not even giving him a transplant will improve. A palliative transplant is not done because a liver is not used for that and because the patient is not subjected to an intervention, such a demanding anesthesia and postoperative period in which you can die", says Calleja.

"

in which all the professionals involved participate: surgeons, anesthetists, medical specialists, pathologists, coordinators, psychiatrists... and each candidate is evaluated in those situations," he adds.

Specialists argue that the incorporation of new indications is complicated.

"There are patients who were in a gray zone and now we include them because we think they can benefit from the drop in hepatitis C patients," says Calleja.

In this regard, Turrión believes that these patients accounted for 40% of transplants and now that they disappear there is room for new indications.

, transplants due to tumor pathology,

has been established . In hepatocarcinoma it is clear and

. There are the criteria of the University of California in San Francisco, which practically accepts them a lot of people, and then there are other indications

".

Turrión explains that in Norway they have more donors than recipients and that is why they have tried to implement indications that are not the conventional ones.

"Scientific evidence has shown that a well-selected group of patients with liver metastases from colorectal cancer have obtained very good results and protocols are already being established. In fact, here in Spain a protocol is going to be led from La Fe de Valencia in which patients can be included.There are other tumors, with

, which are also contemplated, and a tumor that has always been a demon for liver transplantation,

, that it is a carcinoma and that it had very bad results, but that it has been shown with a protocol that was established in the Mayo Clinic that good results are also obtained.

A little out there goes the extension of the new indications.

I think

because we can find that we transplant patients with metastases and perhaps patients with benign pathologies miss the boat because of course we know de facto that they are going to have much better results with a lot of better survival."

Treatment for the C virus, a turning point

"In the lists of 10 years ago, 60-70-80% were virus C. With the treatment of the virus that has disappeared. It seems to me a spectacular thing and it is not insisted enough", comments Manuel Jiménez.

"

and I sincerely believe that it will be studied as a model of unrepeatable change in health, probably because it was a disease discovered in the 1990s that became lethal for hundreds of thousands of Spaniards, and in four or five years this situation has been brutally reversed," Calleja stresses.

"Just as I say that, I say that

until a certain moment when it gets angry, it has a limit. But it is very grateful, the patient who has liver disease due to alcohol and leaves due to drinking or obesity and loses weight, that patient becomes a normal person. In other words, the capacity we have to act in health with these patients is much greater than perhaps in a heart or a kidney because the liver

", Calleja expands.

File photo of the center.

Since 2015, when the treatment emerged,

, which has reduced the number of people admitted for terminal liver failure due to the C virus and people on the waiting list for transplantation (up to 300 inclusions less per year).

In addition, it has also allowed C virus positives to be organ donors, even for negative recipients, being able to receive treatment and not develop the disease.

The profile of the donor and the recipient

The donor profile has also evolved remarkably over the years.

Decades ago they were basically

, thanks also to the longer life expectancy.

"When more patients began to enter waiting lists, more donors were needed and new sources had to be explored. At that first moment we did not want people over 60 years of age, and now more than 60% are over 60 years of age, almost 30% is over 70 years old and up to 5% are over 80," says Turrión.

This already retired specialist points to the establishment of the road safety law.

"With the speed limits, the mandatory use of a helmet, etc., the donor profile has completely changed, fortunately, because I believe that it is a very bad investment to exchange cirrhotic livers or livers with tumors for healthy organs from young people aged 22, 17 and even 16 years as I extracted many due to traffic accidents".

The age of the recipients has also changed.

Normally they were patients who had little extrahepatic pathology, that is, there were no heart or lung problems, etc.

"The most serious were selected, but within that, those who had the best chance of surviving, there was an age limit," says Cuervas-Mons.

In contrast,

and in addition to liver disease,

.

Technology to optimize livers

Between 25 and 30% of the livers offered for donation are not used.

The donors are older and the livers are more suboptimal.

To increase the number of donors that can be used because they are still few and also out of respect for the families of the donors who have given their acceptance, so that these organs are really useful, they have machines to optimize, revitalize these livers (taking advantage of the regeneration capacity of this organ) and that it also arrives in the best conditions to the recipient after coming from a long journey or depending on what conditions.

In this way, for example, donors who have fatty liver can recover once that liver is optimized.

As?

"We do ex situ or ex vivo dynamic preservation, which is called. We use an ex situ liver perfusion machine that we have had since 2021, through which we pass the livers of donors over 65 years of age or who have other problems to optimize them before implanting them. In Spain we usually use regional normothermic [body temperature] preservation, but we are starting to use this method. In fact, a regional laboratory has been created in Madrid to collaborate with the four existing liver transplant units. The idea is to also collaborate with other centers in Spain, so that they can start using these techniques", explains Alberto Pueyo, surgeon at the Liver Transplant Unit.

"We have a project for oxygenated hypothermic perfusion or dynamic cold preservation. It is a technique that is not yet standardized and is yet to be evaluated. Once extracted from the donor, we put the liver in a machine in which a preservation liquid circulates, which it passes through the liver and oxygenates it. The liver is one of the most sensitive organs to ischemia [lack of blood supply] and this machine allows the organ to be oxygenated while it is not being placed in the recipient," explains Pueyo, who adds that it already there is scientific evidence in Europe, especially for donors in asystole, and in the Puerta de Hierro they have already transplanted nine livers in perfusion.

"We are among the first to be doing it continuously in clinical practice. It does not replace what we already do, normothermic regional perfusion, but, apart from being able to use livers that are good and may have been discarded, it is easier and more It allows you to get into the habit and then do another more complex procedure, such as normothermia. It can be useful for hospitals that want to later switch to hot perfusion," reflects Pueyo.

This surgeon emphasizes that right now "there is a lot of research with these machines. For example, for steatosis [fatty liver], there is a lot and there is no magic cocktail that cures it. Research is being done on whether it can be reversed or improved organ with steatosis by placing it in a machine for a while. It is one of the challenges, but it is not yet a reality".

Another possible application is to 'grow' the organ.

"All donors in Spain under the age of 35 are offered for a child recipient, but the part of the liver that is left over by the child is offered for an adult and we put a piece because it is normally enough. If it were not enough, it could be put in for a while in a machine 'feeding' it to achieve sufficient capacity to implant. But this is not real today", concludes Pueyo.

The challenges of liver transplantation

Several decades ago, one of the main challenges was avoiding rejection.

The patients needed corticosteroids, which have other side effects.

"Today we have much more powerful drugs to prevent rejection and with fewer side effects. Chronic rejection, which is a major problem in the heart, kidney and lung, and in the liver is less than 3%. The retransplant rate due to rejections it is practically negligible and due to recurrence of the original disease, it is practically anecdotal", explains Cuervas-Mons.

By reducing rejection and not needing corticosteroids, the incidence of infectious complications has decreased.

"With immunosuppressant medication, when the immune system was depressed, viruses that we have latent, such as cytomegalovirus (80% of adults have it latent), were reactivated, and mortalities occurred.

"Immunosuppressants and anti-infectives of all kinds have been key to controlling the postoperative period of these patients. Now the challenges are completely different. We find patients who no longer go to the transplant as healthy as before. Right now diabetic people go, even some who they have ischemic heart disease, obesity, kidney failure... and the state after the transplant is not completely healthy, they are patients who have to take immunosuppressants, which have side effects, which brings us to the two situations that worry us the most: monitoring for cardiovascular disease that these patients have, which is increasing. That is, they die of the same causes as the general population, but more since these medications increase arteriosclerosis, produce hypertension...", indicates Calleja.

The other situation, adds Calleja, is "the appearance of tumors from another organ, since immunosuppressants also increase the rate of tumors and require surveillance programs in a more systematic way than the general population."

Another current challenge is the expansion of indications for transplantation, such as those with liver metastases from colorectal cancer, as already mentioned, or other types of tumors.

zero alert cases

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For Reyes Iranzo, coordinator of the Surgical and Anesthesia UCI at Puerta de Hierro, "currently the most complex transplants are sometimes

, in a terminal clinical situation of dying if an organ does not appear "Because the liver generates many functional disorders in the body and if you don't solve it in a 24-hour period, the patient dies. I believe that now the biggest challenge is those receptors, the patients on zero alert. Also retransplants."

These severe acute liver failures

.

"In Spain it is not very frequent because a prescription is needed and access is more restricted, but in countries like the United Kingdom it is sold in supermarkets and gas stations, they buy it and take it over a certain amount and it is a frequent cause of liver failure. severe (it is the most common cause of fulminant liver failure in the United Kingdom and the USA, 57% of cases)".

Calleja adds that what we have here every year is "some cases of

, such as

, and more and more we have cases of people taking

and they also cause that kind of severe liver failure," adds Calleja.

According to the criteria of The Trust Project

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