Liver transplantation: procedure, forecast

Liver transplantation takes the 2nd place among transplantation of solid organs. The indications are cirrhosis of the liver (70% of transplants in the US, 60-70% of which are associated with hepatitis C); fulminant liver necrosis (about 8%); hepatocellular carcinoma (about 7%); atresia of bile ducts or metabolic disorders, mainly in children (about 3%) and other cholestatic (for example, primary sclerosing cholangitis) and noncholestatic (autoimmune hepatitis) disorders (about 8%). For patients with hepatocellular carcinoma, transplantation is indicated for one tumor less than 5 cm or up to 3 tumors less than 3 cm (the Milan test) and for certain fibrolamelar tumor types. In patients with metastases in the liver, transplantation is indicated only with neuroendocrine tumors in the absence of extrahepatic growth after removal of the primary tumor.

Absolute contraindications are increased intracranial pressure (> 40 mm Hg) or low cerebral perfusion pressure (<60 mm Hg), sepsis, in advanced stages or metastatic hepatocellular carcinoma; all these conditions lead to adverse outcomes during or after transplantation.

Almost all donor organs are obtained from donor corpses with a beating heart, suitable for the AB0 system and for the size of the liver. Annually about 500 transplants are obtained from live donors who can live without a right lobe (for transplantation from an adult to an adult) or without a lateral segment of the left lobe (for transplantation from an adult to a child). The advantages of a living donor for the recipient include a shorter waiting time, a shorter period of cold ischemia for the implanted organs, and the ability to schedule transplant times optimally for the patient's condition. Disadvantages for the donor are the risk of death at a frequency of 1: 300-1: 400 (compared with 1: 3300 when taken from live kidney donors) and complications (especially leaking of bile) in 1/4 cases when resection of the lobe, rather than segmental resection. Live donors are at risk of psychological pressure. A number of organs are obtained from donors who died not from heart disease.

The risk factors for the recipient associated with the graft (from live donors or donors-corpses) include the age of the donor over 50 years; steatosis of the liver; elevated levels of hepatic enzymes, bilirubin, or both; prolonged stay in the intensive care unit; hypotension, requiring the use of vasoconstrictor drugs; hypernatremia. Transplantation from a female donor to a male recipient also increases the risk. But, since the imbalance between needs and resources for liver transplantation is large enough (and continues to increase because of the spread of cirrhosis associated with hepatitis), organs from donors over 50 and with a short cold-ischaemia time, organs with fat infiltration and organs with viral hepatitis (for transplantation to recipients with cirrhosis, induced by viral hepatitis). Additional technologies for increasing organ resources include separation of the hepatic transplant, when the liver of the deceased donor is divided into right and left lobes or the right lobe and the left lateral segment (conducted in or ex situ) and distributed between the two recipients; and a domino transplant rarely used, in which the liver of the donor corpse is transplanted to the recipient with infiltrative diseases (eg, amyloidosis) and the explanted diseased liver is transplanted to an elderly patient who can live with the diseased liver, but is not expected to survive long enough for the manifestation of adverse effects of graft dysfunction.

Despite these innovations, many patients die waiting for transplants. Liver-preserving techniques (extracorporeal perfusion by suspensions of cultured hepatocyte cultures or long-lived hepatoma cell lines) are used in some centers to maintain the life of patients until a suitable liver is found or acute dysfunction is resolved. To optimize the distribution of available organs, a prognostic index is calculated for patients on the national list, which depends on the level of creatinine, bilirubin, MHO (for adults) and age, serum albumin, bilirubin, MHO, growth rates (for children). For patients with hepatocellular carcinoma, this parameter includes the size of the tumor and the waiting time (it increases with each component increase). Patients with higher indices have a higher probability of dying, and they have advantages in obtaining organs from donors corresponding in weight and ABO system.

[1], [2]

Procedure of liver transplantation

The liver of donor corpses is removed after laparotomy examination of the abdominal cavity, confirming the absence of diseases of the abdominal cavity organs, which can interfere with transplantation. Live donors perform fractional or segmental resection. The implanted liver is perfused and stored in a cold canning solution no more than 24 hours before transplantation; with increasing storage time, the incidence of graft failure and damage to the biliary system of the ischemic type increases.

Hepatectomy in the recipient is the most traumatic part of the procedure, as it is often performed in patients with portal hypertension and blood clotting disorders. The loss of blood during surgery can be more than 100 units, but the use of cell-preserving equipment and autotransfusion techniques can reduce allogeneic transfusion needs to 10-15 units. After hepatectomy, an anastomosis is formed between the superhepatic vena cava of the donor transplant and the inferior vena cava of the recipient in the "end-to-side" type (piggy-back method). An anastomosis is then formed between the portal veins of the donor and recipient, the hepatic arteries and the bile ducts. With the help of this technology, there is no need to use an artificial circulation device to direct portal venous blood into the systemic venous blood flow. Heterotopic location of the liver provides the presence of an "additional" liver and helps to avoid some technical difficulties, but the results are unsatisfactory, therefore this technology is in the experimental development stage.

Rates of immunosuppressive therapy may vary. Usually, on the day of transplantation, monoclonal antibodies of the IL-2 receptor with calcineurin inhibitors (cyclosporin or tacro-limus), mycophenolate mofetil and glucocorticoids are assigned. With the exception of recipients with autoimmune hepatitis, in most patients the dose of glucocorticoids decreases within a few weeks and often their reception ends after 3 to 4 months. In comparison with the transplantation of other solid organs, liver transplantation requires the appointment of the lowest doses of immunosuppressants.

For unknown reasons, liver allo-transplants are rejected less aggressively than allografts of other organs; hypererostal rejection is less frequent than expected in patients previously sensitized to HLA and ABO antigens, and the dose of immunosuppressants can often be reduced relatively quickly and their reception is actually stopped. Most cases of acute rejection proceed easily and self-stop, are noted in the first 3-6 months and do not threaten the survival of the transplant. Risk factors for rejection are the young age of the recipient, the elderly age of the donor, significant differences in the HLA system, prolonged cold ischaemia and autoimmune disorders; The worst state of nutrition (for example, with alcoholism), apparently, has a protective effect.

Symptoms and objective signs of rejection depend on its type. Symptoms of acute rejection are noted in almost 50% of patients; symptoms of chronic - in 2%.

Differential diagnosis of acute rejection is carried out with viral hepatitis (eg, cytomegalovirus, Epstein-Barr virus, recurrent hepatitis B, C or both,), intoxication with calcineurin inhibitors, cholestasis. In the event that the diagnosis is difficult to establish clinically, rejection can be diagnosed by percutaneous puncture biopsy. Alleged rejection is treated by intravenous administration of glucocorticoids; antitimocytal globulin and OKTZ are the drugs of choice in the event that glucocorticoids are not effective (at 10-20%). Retransplantation is performed in the event that rejection is refractory to immunosuppressants.

Immunosuppressants contribute to the development of recurrences of viral hepatitis in patients who had prior to transplantation liver cirrhosis associated with viral hepatitis. Hepatitis C recurs in almost all patients; usually viremia and infection occur subclinically, but can be the cause of acute hepatitis and cirrhosis. The risk factors for the development of re-infection include certain characteristics of the recipient (elderly age, type HLA, hepatocellular carcinoma), the donor (elderly age, fatty liver, long ischemia, live donor), virus (large viral load, genotype 1B, on interferon), as well as factors that arise after the procedure (doses of immunosuppressants, treatment of acute rejection of glucocorticoids and OKTZ, cytomegalovirus infection). Standard treatment (see page 204) is ineffective. Hepatitis B recurs in all, but is successfully treated with immunoglobulin and lamivudine; co-infection with hepatitis D, apparently, 1Q mu, provides protection against relapse. 'V

Early complications (within 2 months) of liver transplantation include a primary impairment of function in 5-15% of cases, biliary dysfunction (eg, ischemic strictures of anastomoses, leaking of bile, duct obstruction, effusion around the T-tube) in 15-20%, thromboses portal vein at 8-10%, hepatic vein thrombosis in 3-5% (especially in patients receiving sirolimus), mycotic hepatic artery or its pseudo-aneurysm and rupture of the hepatic artery. Typical symptoms are fever, g-potency, increased levels of liver enzymes.

The most frequent late complications are strictures of intrahepatic or anastomotic bile ducts, which manifest themselves with symptoms of cholestasis and cholangitis. Strictures are sometimes treated endoscopically or through percutaneous transhepatic cholangiographic dilatation, stenting, or both, but often these complications require re-transplantation.

Prognosis of liver transplantation

During the first year, the survival rate when using the liver of live donors is 85% for patients and 76% for transplants; and when using the liver of donor corpses, 86% and 80%, respectively. The overall survival rate for patients and transplants, respectively, is 78 and 71% for the 3rd year and 72 and 64% for the 5th year. Survival is more common in chronic liver failure than in acute liver failure. The death of a patient after the expiration of 1 year is rare and is more likely a consequence of relapsing diseases (for example, cancer, hepatitis) than post-transplant complications.

Recurrent hepatitis C leads to cirrhosis in 15-30% of patients for 5 years. Liver disorders associated with autoimmune diseases (eg, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) recur in 20-30% of patients for 5 years.