После операции

Прежде всего, докторам надо убедиться в функциональной состоятельности трансплантата. Она оценивается по нормализации факторов свертывания крови и уровня трансаминаз (печеночных ферментов), а также достижению устойчивой гемодинамики.

К сожалению, в ряде случаев наблюдается реакция острого отторжения. Она возникает в первые 3 месяца после операции, но в большинстве случаев ее наблюдают на 4-14 дни после трансплантации. Иногда она проходит бессимптомно. Но значительно чаще ее признаками являются увеличение и болезненность пересаженной печени, лихорадка, светлый цвет кала и желтуха. Так же об этом свидетельствует повышение уровня билирубина (см. рубрику «Словарь пациента»), трансаминаз и выраженный лейкоцитоз.

Для борьбы с реакцией отторжения предусмотрены весьма серьезные мероприятия. Именно на это направлена так называемая иммуносупрессивная терапия. Она вынужденно подавляет иммунный ответ организма, пытающегося изгнать «чужеродный», по его мнению, трансплантат. Как и любая другая иммуносупрессивная терапия, она проводится на фоне активного лечения стероидными (см. рубрику «Словарь пациента») препаратами.

С открытием в 1980 году циклоспорина, одного из главных и по сей день иммуносупрессорных препаратов, началась новая эра в транспланталогии. Выживаемость реципиентов резко повысилась. С совершенствованием иммуносупрессивной терапии и связаны главные надежды ученых.

Самое важное в ней - удержать равновесие между иммуносупрессией и сохранением организмом возможности сопротивляться инфекциям. Если дозы препаратов подобраны правильно, острая реакция отторжения возможна, но всегда обратима. Именно в этом и состоит главное искусство врача – пройти по тонкой линии между этих двух огней. И немецкие медики весьма поднаторели в этом непростом деле, ведь это искусство приходит с опытом, а опыта докторам в Германии не занимать!

Если дозы иммунодепрессантов слишком велики, больной может умереть от тяжелых инфекционных осложнений, а если слишком малы – то всегда есть опасность отторжения трансплантата. Механизм действия циклоспорина заключается в подавлении ранней фазы активации Т-лимфоцитов, одного из главных компонентов иммунной системы. Он до сих пор успешно применяется, но его побочные действия весьма негативны для организма.

Еще более сильный препарат такролимус. Он имеет такой же механизм действия, как и циклоспорин, но по силе превосходит его в 10-100 раз. Поначалу его назначали тем, кому не помогал циклоспорин. Но в последствии выяснилось, что наиболее оптимальные результаты дает комбинация этих двух препаратов, как по эффективности борьбы с отторжением, так и по минимизации побочных действий. Отчасти это основано на том, что такролимус лучше всасывается в кишечнике, и потому его эффект более предсказуем. Спектр побочных эффектов у обоих препаратов примерно одинаковый. Наиболее частые побочные эффекты такролимуса - нефротоксический и нейротоксический (судороги, тремор, эпиприпадки).

Великолепное подспорье в лечении осложнений, связанных с отторжением трансплантата, оказывает сравнительно недавно вошедшее в практику использование моноклональных антител. Самым известным и нынче широко применяемым из них является муромонаб-CDЗ, препарат, состоящий из мышиных моноклональных антител к Т-лимфоцитам человека. Эти антитела избирательно воздействуют на специальные рецепторы Т-лимфоцитов, блокируют их пролиферацию (см. рубрику «Словарь пациента»), и подавляют их воздействие на трансплантант. Препарат дает сравнительно небольшие побочные эффекты. Особенно действенен он в комбинации с традиционными цитостатиками.

Большие надежды ученые Германии связывают с введением в медицинскую практику препарата сиролимус или рапамицин. Его формально так же можно отнести к группе традиционных цитостатиков, но его фармакологическое действие отличается от такролимуса. Комбинация сиролимуса с циклоспорином и такролимусом позволяет усилить иммуносупрессивный эффект при одновременном снижении дозы препаратов и уменьшении побочных действий.

В настоящий момент в Германии идет активная разработка всевозможных видов моноклональных антител. Ученые считают, что именно их использование поможет в дальнейшем действовать в иммуносупрессивонй терапии узконаправленно и подавлять только те Т-лимфоциты, которые «воюют» с трансплантатом. В настоящий момент уже созданы и активно используются такие препараты как даклицумаб и базилихсимаб, состоящие из человеческих белков, действующие аналогично муромонабу-CDЗ, но имеющие точкой приложения другие клеточные структуры в Т-лимфоцитах.

Комбинированное использование всех этих медикаментов позволяет значительно снизить опасность отторжения пересаженной печени. Кроме этого, достоверно установлено, что, к сожалению, использование циклоспорина и такролимуса увеличивает риск онкозаболеваний в отсроченном периоде. И уменьшение их дозы, в итоге, сказывается положительно на здоровье пациента.

ПРОГНОЗЫ

Прогнозы для больных с пересадкой печени в последние 10-15 лет резко изменились, выживаемость их в настоящее время увеличилась более чем в два раза. По данным трансплантационного центра в Берлине, где выполняется более 150 трансплантаций печени в год, общие цифры проживших 10 лет после трансплантации в возрасте до 45 лет – 66 %, после 60 лет – 50%. В течение года прогноз положителен для 83 % пациентов, перенесших операцию.

Вообще же, разброс цифр благоприятных прогнозов очень велик. Необычайно многое зависит, например, от состояния больного на момент операции. Среди больных, сохранивших к моменту операции работоспособность, годичная выживаемость составляет 85%; а вот среди попавших на операционный стол из отделения реанимации - всего 50%. Из этого следует – с операцией не следует тянуть, и длительное ожидание донорского органа изрядно ухудшает шансы на благоприятный исход.

Также большое значение имеет принадлежность больного к группе высокого или низкого риска. К группе высокого риска относят больных с онкологическими заболеваниями печени, гепатитом В, острейшими формами гепатита, с почечной или легочно-сердечной недостаточностью. Все остальные – это группа низкого риска. Годичная и пятилетняя выживаемость в группе низкого риска составляла 90% и 87%, в группе высокого риска – 60% и 35%, соответственно.

Как правило, качество жизни больных, переживших трансплантацию печени, вполне удовлетворительное, очень многие сохраняют трудоспособность. К сожалению, больным с пересаженной печенью приходится пожизненно принимать иммуносупрессивные медикаменты.

Liver transplant - one of the most complex and difficult operations in the modern transplantology. It is entirely determined by the role of the liver in our body, and anatomical location and its blood supply. But at the same time, the quantity and quality of the operations is growing rapidly year by year. And now a liver transplant, 15 years ago, is considered unique in its complexity surgery, in fact, put "on stream" in the specialized centers in Europe and America. Of course, it remains extremely important problem of finding a suitable material for transplantation that is - of donor organs, and this will be discussed in detail below. But in spite of that, as a result of tremendous progress and development of the techniques of liver transplant operations, it is currently ranked second in the world in terms of the frequency of execution after renal transplantation.

In Russia, a liver transplant is not so common in medical practice. There are a number of reasons: it is the complexity of the operation, it is the need of special equipment for it, and the problem is related to the search of donor organs, this and subsequent adequate immunosuppressive therapy, which requires a completely extraordinary conditions. But in Germany, the number of liver transplants in a year amounts to many hundreds, and liver transplantation is - regular medical routine. Naturally, during such a large number of operations and honed the skill of surgeons currently displayed on a fantastic level.

Indications and contraindications

Indications for liver transplantation are quite simple: it is a violation of its functions to the extent that does not provide the vital needs of the body. It may come as a result of a variety of diseases, but above all, it - the outcome of various types of cirrhosis. As practice shows, on average, all forms of cirrhosis are responsible for the implementation of about 70% of liver transplantation. There is nothing surprising in this - in the developed countries, cirrhosis is the third leading cause of death in patients aged 45-65 years (after cardiovascular diseases and tumors), well, the most common cause leading to cirrhosis is alcohol abuse. In second place on the list of causes of cirrhosis are viral cirrhosis caused by chronic hepatitis B.

But, by and large, there is no difference which of the many diseases of the liver led to its functional failure. Much more important is the extent to which the body is at the time of transplantation and the expediency of its holding.

All contraindications for liver transplantation are divided into absolute and relative. First of all, to the absolute contraindications are untreated liver diseases such as viral hepatitis B and C, Epstein-Barr disease, toxoplasmosis, that is, diseases that a liver transplant and can continue their destructive effect on the graft. Very poor results delayed giving a liver transplant in the bile duct carcinoma and metastatic spread. Just a liver transplant is impractical to do with severe comorbidities such as severe cardiopulmonary disease, brain damage, severe failure of function of other organs.

Old age is not a contraindication for surgery. What matters it is only the patient's medical condition and the presence of a concomitant disease. Thus, old age can be conventionally regarded as a relative contraindication, and then - on a common set of factors. For relative contraindications also include portal vein thrombosis prior to complex surgical interventions on the liver and bile ducts, and kidney failure.

Donor liver

Apart from the complexity of the surgery, a major problem for liver transplantation is the presence of the donor organ. It may be obtained as from a deceased or from a living donor. First, in most cases the liver came from deceased donors, but now this situation is changing. The absolute prerequisite for transplantation is the lack of a donor prior serious illness, and most importantly, recipients and donors should approach each other by blood group. The survey is carried out as thoroughly as possible the donor, to the best of extreme conditions. Recently shortage of donor organs has led to a huge queue waiting for a liver transplant. Today, therefore, are increasingly turning to a liver transplant from a living donor, usually a relative of the patient. The possibility of the liver transplant from a living person based on the fact that the liver is the only organ that has an amazing ability to repair itself. This is what underlies the liver transplant from a living donor, and after a transplant, and the remaining portion of the donor liver will grow to normal size for several weeks. This option is transplantation was first used in 1989 in Japan, due to the shortage of donor organs in children with end-stage liver disease. But since 1991, this technique has been used extensively in Europe. As you know, a liver transplant from a living donor immediately relieves a lot of problems, and helping save the lives of many lyudey.K The advantages of this technique include the ability to plan operations and thorough preparation for the transplant. As a rule, in the case of a liver transplant from a living donor is used left lobe of the liver. Of course, there must comply with the measure, since there is always a risk as "deprive" the volume of transplant recipient, and "leave" the donor is too small "piece" of the liver. But these complications are extremely rare elegance with today's techniques.

When selecting a donor clinics in Germany, produces extremely serious examination of the liver transplant to be. First of all, the blood is tested compatible donor and recipient antigens AB0. Typing tissue antigens of HLA (human leucocyte antigens - histocompatibility antigens) is not carried out, and the presence of cytotoxic anti-HLA antibodies does not preclude the transplantation.

I must say that the age limit for donation is not defined. Much more important is the functional state of the liver, which is detected by careful examination. For prospective donor developed an extensive list of studies, most of which is an MRI of the liver and its blood vessels, allowing the details to clarify the course of the proposed transaction. After all, when a liver transplant from a living donor, he is also exposed to some danger, and carried out the survey allow us to reduce the risks to a minimum.

The selection of a suitable liver transplant - it is extremely responsible. In the history of transplantology center in Essen were cases when for liver transplants were considered candidates 12 relatives of the patient and out of this number was chosen only one "worthy." There are cases where the donor suffers selected by some concomitant diseases. In preparation for the transplant, these ailments were treated carefully, and transplant is almost healthy liver.

By and large, all this makes liver transplantation from a living person most promising and technically, and prognostic, and even in the moral aspect. Of particular relevance to this issue and give the latest research of scientists from Essen to develop a methodology of accelerated immunization donor against viral hepatitis B and C, giving a significant part of cirrhosis requiring transplantation. This allows the transplanted liver is already immunized, capable of dealing with the consequences of malicious hepatitis and it can also be a serious argument in favor of a liver transplant from a living donor.

The very selection of the liver from a living donor is not as traumatic as you can imagine the person far from medicine. The normal liver is separated into several fractions which are sufficiently delineated formation. So I do not think that surgery is necessary to separate part of her slit "of the living." This considerably reduces the complexity of the operation and to avoid unnecessary bleeding and expiration of bile.

OPERATION

As mentioned above, the operation of a liver transplant is a severe, traumatic and usually accompanied by a massive blood loss. Moreover, it continues from 5 to 8 hours on average. The liver is very well supplied with blood, and any intervention on it this volume leads to an almost complete overlap of the circulatory system in the area. In order to avoid stagnation, surgeons formed workarounds circulation, bypassing the liver vessels. Improving these techniques, and to make it possible liver transplant nearly routine operations. But even in this situation, blood loss in interference can be significant. Taking into account the possible need for a blood transfusion, it prudently harvested in the preoperative period, most of the fence from the patient, which allows to accumulate a sufficient amount of blood.

Technique surgery for a liver transplant is very complicated, and we can not describe it in detail as part of our short article. One can only say that her technique honed to perfection in the major transplant centers in Germany and the number of complications it is now quite significantly reduced.

The state of health of the patient in the early postoperative period depends on the sustainability gemodinamiki.Estestvenno, posleopertsionnye patients are in the intensive care unit for 2-4 days and then transferred to the transplant ward. Length of stay in hospital after liver transplantation in Germany about 10-20 days.

Complications of surgery primarily manifested in the possibility of bleeding. After all, their reason is not only the trauma of intervention, but also observed in all patients with liver disorders of the clotting factor, called coagulopathy.

But the consequences of surgery - this is, unfortunately, not everything should be wary of doctors and patients. Much more dangerous long-term complications associated with the body's reaction to the transplant.

AFTER OPERATION

First, doctors need to make in the functional viability of the transplant. It is estimated to normalize the clotting factors and the level of transaminases (liver enzymes) as well as the achievement of a stable hemodynamics.

Unfortunately, in some cases, there is a reaction of acute rejection. It occurs in the first 3 months after surgery, but in most cases it was observed 4-14 days after transplantation. Sometimes it is asymptomatic. But more often its symptoms are pain and increase the transplanted liver, fever, light color stool and jaundice. As evidenced by elevated bilirubin levels (see. Section "Dictionary of the patient"), transaminases, and marked leukocytosis.

To combat the reaction of rejection includes very serious event. It is the objective of the so-called immunosuppressive therapy. She is forced to suppress the body's immune response, trying to expel "foreign", in his opinion, the transplant. As with any other immunosuppressive therapy, it is held against the backdrop of the active steroid treatment (see. Section "Dictionary of the patient") drugs.

With the discovery of cyclosporine in 1980, one of the main and still immunosuppressive drugs, a new era began in transplantology. The survival rate of recipients has risen sharply. With improvements in immunosuppressive therapy and the associated main hopes scientists.

The most important thing in it - to keep the balance between immunosuppression and the possibility of preserving the body fight infections. If dose regimens are chosen correctly, acute graft rejection is possible, but always reversible. That this is the most important art of the doctor - walk a fine line between these two fires. And the German doctors is very adept at this delicate matter, because this art comes from experience, and experience of doctors in Germany do not hold!

If the dose of immunosuppressive drugs are too large, the patient may die from severe infectious complications, and if too small - there is always a risk of transplant rejection. The mechanism of action of cyclosporine is to suppress the early phase of T-cell activation, one of the main components of the immune system. He still used successfully, but its side effects are very negative for the organism.

Even more powerful drug tacrolimus. It has the same mechanism of action as cyclosporine, but it is superior in strength in the 10-100. At first it was prescribed for those who are not helped cyclosporine. But afterwards it was found out that optimal results are obtained by a combination of the two drugs, both in the response to the rejection, and to minimize side effects. This is partly based on the fact that tacrolimus better absorbed in the intestines, and because of its effect is more predictable. The range of side effects in both drugs about the same. The most frequent side effects of tacrolimus - nephrotoxic and neurotoxic (convulsions, tremor, epipripadki).

A great help in the treatment of complications associated with graft rejection, has relatively recently joined the practice of the use of monoclonal antibodies. The best known and now widely used of these is muromonab-CDZ, preparation consisting of murine monoclonal antibodies to human T-lymphocytes. These antibodies selectively act on specific receptors of T lymphocytes, blocking ihproliferatsiyu (see. Section "Dictionary of the patient"), and inhibit their impact on transplant. The preparation provides a relatively small side effects. It is especially effective in combination with conventional cytotoxic drugs.

Great Expectations German scientists associated with the introduction into medical practice of the drug sirolimus ilirapamitsin. His formal can also be attributed to the group of traditional cytotoxic drugs, but its pharmacological action differs from tacrolimus. The combination of sirolimus with cyclosporine and tacrolimus allows for enhanced immunosuppressive effect while reducing the doses of drugs and reducing side effects.

Currently, in Germany there is an active development of various types of monoclonal antibodies. Scientists believe that their use will help in the future to act immunosupressivony therapy and specific and inhibit only those T cells that are "at war" with the transplant. At the moment already established and widely used drugs such as daklitsumab and bazilihsimab composed of human proteins acting similarly to muromonab-CDZ, but with the point of application other cellular structures in T-lymphocytes.

The combined use of these drugs can significantly reduce the risk of rejection of the transplanted liver. Moreover, well established that, unfortunately, the use of cyclosporin and tacrolimus increases the risk of cancer in the delayed period. And decrease their doses, as a result, a positive impact on the health of the patient.

FORECASTS

Predictions for liver transplant patients over the last 10-15 years has changed dramatically, their survival is now increased by more than twice. According to the transplant center in Berlin, where he performed more than 150 liver transplants a year, the overall figures have lived 10 years after the transplant before the age of 45 years - 66%, after 60 years - 50%. During the year, the forecast is positive for 83% of patients undergoing surgery.

In general, the spread of numbers favorable forecasts is very high. Unusually, much depends, for example, the patient's condition at the time of surgery. Among patients retained at the time of the operation performance, one-year survival rate is 85%; But among the fallen on the operating table of the intensive care unit - only 50%. It follows - with the operation should not pull, and the long wait for a donor organ considerably worsens the chances of a favorable outcome.

Also of great importance is the patient belonging to the group of high or low risk. High risk include patients with liver cancer, hepatitis B, acute form of hepatitis, renal or pulmonary heart disease. All the rest - a group of low-risk. One-year and five-year survival rate in the low-risk group was 90% and 87% in the high-risk group - 60% and 35%, respectively.

As a rule, the quality of life of patients with post-liver transplantation, is quite satisfactory, many remain disabled. Unfortunately, patients with liver transplant is necessary for life to take immunosuppressive medications.

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