The liver is a sufferer. Sometimes it gets so bad that it becomes almost useless, needing to be replaced as soon as possible. After all, you can’t live more than a few hours without counting on the work of this organ, a handyman in the human body.
Under normal conditions, without hesitation, it is able to break molecules to be used or thrown away, store important substances, manufacture proteins, send energy to the whole organism, destroy microbes absorbed with food if they have bypassed the intestinal defenses, eliminate aged blood cells and more.
But Brazil, in this case, is the second country in absolute number of liver transplants on the planet, second only to the United States. In 2019 — the latest data we have at hand —, of the 23,957 transplants performed in the country, 2,245 were liver.
Quite an increase, since only 1,603 of these surgeries had taken place ten years earlier. Just as the number of teams capable of performing the procedure has grown and, yes, the number of donors has increased a lot as well.
Even so, in that 2019 it would take 2,967 surgeries to close the queue. A sign that 722 people were on hold. Some stay there for up to four years. Others do not support. And this situation of repressed demand tends to get worse, because there is no longer a donated liver around like it used to be.
With an aging population that has more and more obesity and other diseases, the donated organ often arrives damaged, with damaged vessels and fat accumulation. If it wasn’t for that, those more than 700 patients would not have been left out. Well, there were more deceased donors than people in need of transplants. But four out of ten livers were simply not in good condition to be transplanted.
This is, in fact, the problem that a study led by liver transplant surgeon Yuri Longatto Boteon, from Hospital Israelita Albert Einstein, in São Paulo, intends to minimize by testing a technique known as HOPE, an acronym for “hypothermic oxygenated machine perfusion” or oxygenated hypothermic perfusion machine.
What to expect from this kind of technique
Yesterday I spoke with the surgeon directly from Istanbul, Turkey, where the ILTS (International Society for Liver Transplantation) congress took place.
“The use of perfusion machines had been considered in the first transplants almost fifty years ago, but the ice box to carry the donated organ was simpler and worked well. That’s why it’s only now become the subject of the time”, me he said. It could: the difficulty in finding a donor in perfect condition has become commonplace.
Alternatives such as the HOPE technique tested at Einstein increase the time the organ remains ready to be transplanted, which is very encouraging in our case, when huge distances can exist between the donor who is in the north of the country and the recipient who is in the south. But not only that.
Such a perfusion machine improves the conditions of a liver that is not perfectly wonderful. “This reconditioning reduces the risk that, after surgery, it will disappoint expectations and not work”, explains Boteon.
There’s more: the technique lessens the threat of the heart having a heart attack during the transplant. Yes, this upper neighbor of the liver, separated only by a muscle, the diaphragm, can be a problem at the moment. HOPE also reduces the likelihood that the kidneys will suffer and that the donated organ will be rejected.
At Einstein, four of the twelve transplants scheduled throughout the study have already been performed. The first, in February, was a 22-year-old boy in critical condition, who could succumb within days. He is now doing well.
Why does the liver suffer so much?
Brazil is not runner-up in liver transplants because it has a worse condition for liver health. “This has more to do with the size of our population and with the fact that, around here, the surgery can be performed in the public network”, explains Yuri Boteon.
Regarding risk factors, they are more or less the same in any corner of the globe, with the largest of them on the rise.
By the way, forget the stigma that the candidate for a liver transplant is always that older individual who has consumed a lot of alcohol. “Excessive drinking is even one of the causes, but it is far from the only one”, guarantees Boteon.
According to him, in Brazil viral hepatitis led the reasons behind the need for a liver transplant. Today, however, both here and in most parts of the world, at the top of the list is non-alcoholic steatohepatitis, the most advanced stage of steatosis, the accumulation of fat in the liver, caused by an increasingly prevalent sedentary lifestyle and obesity. It triggers inflammation that can cause irreversible damage. Sometimes so big that the end of the story is really a transplant.
Other reasons that lead a subject to the waiting list for this surgery are liver cancer and some autoimmune diseases, such as that of the young man who was the first to participate in the Brazilian study.
A liver ready to be donated
Until the 1990s, most transplanted livers came from young people who, unfortunately, had brain death. Now, there is an increase in the supply of older donors who are not 100% and who fit what doctors call extended criteria.
There, a series of details count, from eventual illnesses that these individuals already had to the time they spent in an ICU. “If, there in bed, the organism accumulated sodium, the liver cells may have swelled to the point of being injured”, exemplifies the doctor.
He compares: “If I have an 80-year-old donor who was not obese and who spent only one day in the intensive care unit, his liver will probably be in better condition than someone of the same age who had a serious infection and two weeks hospitalized”.
By criteria like these, when the transplant team perceives a slight possibility that the liver will not function postoperatively, it declines the idea of moving forward.
There is also a race against time. “The liver of a healthy young person is able to wait around twelve hours until it is re-oxygenated by the blood, when it is implanted in the recipient”, says the surgeon. “However, if it is a liver within those extended criteria, the wait shortens to six hours.” This can prevent a donation from the Amazon from serving someone who was on the transplant waiting list in São Paulo.
what are the problems
The thing is, when the liver is removed from the donor, it naturally stops receiving oxygenated blood. This state of ischemia causes your cells to look for an alternative route to oxygen to obtain energy and survive. But the price of this is a brutal production of free radicals.
The detail is that a liver in less than ideal conditions does this with much greater intensity, lowering the chance of success in the endeavor.
“Now, the radicals damage the cell walls and, depending on the amount of tissue damaged, in the end I will no longer be able to transplant that organ”, justifies Boteon.
They also trigger inflammation, with a flurry of molecules called cytokines, experts to dilate the vessels. When the liver is connected to the patient, the accumulation of them spills into the bloodstream and their first stop is usually in the heart, which is just above. “The anesthesiologist, then, is smart because the risk of an arrhythmia is high”, says the surgeon.
In addition, this excess of inflammatory molecules is filtered by the kidneys, which can cause problems in more fragile patients. To complicate matters once and for all, liver cells damaged in this critical period can serve as a target for the immune system, culminating in rejection.
What the machine under test does
The classic ice box to transport the donated organ, by lowering the temperature, leads to cell metabolism to plummet. With this, they spend less energy, depend less on that alternative pathway, consequently generate less radicals and less inflammation as well.
But practice shows that all this reduction is not enough if the donor has such an extended criteria profile. “Currently, it is the case of 60% to 70% of livers used in transplantation”, estimates the surgeon.
With HOPE, however, as soon as the organ is removed, the temperature is maintained between 8 and 12 degrees Celsius, while a liquid with plenty of oxygen is injected through different cannulas. “This alone washes away part of the inflammatory molecules”, points out Boteon. And, in addition to the cold lowering metabolism like the old ice box, the abundance of oxygen minimizes that cascading effect.
The technique, which in Brazil is only being used in research, is already successfully applied in other countries, extending the maximum transport time to eight hours.
What the Einstein study wants to see now is whether there would be markers, that is, molecules in the liver or in the fluid used at HOPE, capable of informing whether everything will work well afterwards, creating a more objective criterion for using or discarding the donated organ. An extra guarantee for patients who have been waiting for him for so long.