Donor selection and liver transplant surgery

The process of selecting donors for liver transplantation is standardized. However, the criteria for "good" or "bad" liver in different clinics are different. The growing need for liver transplantation led to the use of donor organs, which previously could be considered unfit. There was no significant increase in the number of failures associated with poor graft function.

Informed consent is given by the donor's relatives. The age of the donor can be from 2 months to 55 years. The donor of the liver is a person who received a craniocerebral injury, which resulted in the death of the brain.

They support the adequate activity of the cardiovascular system, to carry out the function of breathing, artificial ventilation of the lungs is made. Transplantation of the liver and other vital organs from donors with a contracting heart minimizes the ischemia that appears at normal body temperature and greatly influences the outcome of transplantation.

The donor should not have other diseases, including diabetes and obesity. Histological examination should rule out fat changes in the liver. The donor should not have periods of prolonged arterial hypotension, hypoxia, or cardiac arrest.

Liver transplantation without taking into account the blood group in the ABO system can result in a severe rejection reaction. Such a liver can be used in case of emergency in emergency situations.

It is more difficult to select a donor through the HLA system. It has been proved that incompatibility with certain antigens of HLA class II gives advantages, especially in preventing the development of the syndrome of disappearance of bile ducts.

Donors are examined for markers of viral hepatitis B and C, antibodies to CMV and HIV.

Details of the operation of the donor and recipient are discussed in many works. After isolation of the liver, it is cooled by injection of Ringer's solution through the spleen vein and additionally through the aorta and portal vein 1000 ml of the Wisconsin University solution. Inserted into the distal end of the inferior vena cava can provide venous outflow. After excision, the cooled liver is additionally washed through the hepatic artery and portal vein with 1000 ml of the Wisconsin University solution and stored in this solution in a plastic bag on ice in a portable refrigerator. This standard procedure allowed to increase the storage time of the donor liver to 11-20 hours, made the operation of the recipient "semi-planned" and feasible at a more convenient time. The same surgeon can perform operations at the donor and recipient. Further improvement of organ preservation involves the use of an automatic perfusion device after the liver is delivered to the transplantation center. The viability of the transplant can be investigated using nuclear magnetic resonance.

When selecting a donor liver, it is necessary that it, if possible, fit the anatomical characteristics of the recipient in size and shape. The size of the donor liver should not be greater and, if possible, should not be less than that of the recipient. Sometimes the liver of small sizes is implanted in a large recipient. The donor's liver increases in volume at a rate of approximately 70 ml per day until it reaches the dimensions corresponding to the body weight, age and sex of the recipient.

Operation at the recipient

The average duration of the liver transplantation operation is 7.6 hours (4-15 hours). On average, 17 (2-220) doses of erythrocyte mass are poured. The used apparatus, which recovers erythrocytes, allows to store about a third of the volume of blood poured into the abdominal cavity. In this case, the blood is aspirated and the red blood cells after repeated washing and resuspension are administered to the patient.

Isolate the anatomical structures of the gates of the liver, a hollow vein above and below the liver. The isolated vessels are clamped, crossed, and then the liver is removed.

During the implantation of the donor liver, blood flow in the splenic and hollow vein systems must be interrupted. In the light-hearted period, veno-venous shunting with the help of a pump prevents the deposition of blood in the lower half of the body and edema of the abdominal cavity. Cannulas are placed in the lower hollow (through the femoral vein) and the portal vein, the outflow of blood is carried out in the subclavian vein.

Venovenous bypass allows to reduce bleeding, increase the permissible operation time and facilitate its implementation.

The application of all vascular anastomoses is completed before the restoration of blood flow in the implanted liver. It is necessary to exclude thrombosis of the portal vein. Often there are anomalies of the hepatic artery, and for its reconstruction, donor vascular grafts should be used.

Anastomoses are usually imposed in the following order: the supra-hepatic department of the hollow vein, the papotic section of the hollow vein, the portal vein, the hepatic artery, the bile ducts. Biliary reconstruction is usually performed by applying a choledocho choledohaanastomosis on T-shaped drainage. If the recipient is affected or there is no bile duct, choledochojonostomomy end in the side with the neuromuscular loop turned off by Roux. Before suturing the abdominal cavity, the surgeon usually waits about 1 hour to identify and eliminate the remaining sources of bleeding.

Transplantation of parts of the liver (reduced or divided liver)

Because of difficulties in obtaining donor organs of small size for transplantation, children began to use a part of the liver of an adult donor. This method provides two viable grafts from one donor organ, although usually only the left lobe or the left lateral segment is used. The ratio of the body weight of the recipient and the donor should be approximately 3: 4. In 75% of cases of liver transplantation in children use the reduced donor organ of the adult person.

The results are not as satisfactory as in the whole organ transplantation (the annual survival is 75 and 85% respectively.There are many complications, including increased blood loss during surgery and inadequate blood supply to the graft due to portal portal hypoplasia, graft loss and biliary complications are more common in children, than in adults.

Liver transplantation from a living related donor

In special circumstances, usually in children, the left lateral segment of the liver from a living related donor can be used as a transplant. Living blood donors are blood relatives of the patient who must give voluntary informed consent to the operation. This allows obtaining a transplant in the absence of a cadaveric donor organ. Such an operation is performed in recipients with terminal stage of liver disease or in countries where transplantation of cadaver organs is prohibited. With a high level of surgical technique and anesthesia, as well as intensive care, the risk for the donor is less than 1%. The period of hospitalization lasts an average of 11 days, and blood loss is only 200-300 ml. Occasionally, the donor can develop complications during the operation and after it, for example, damage to the bile duct and spleen or abscess formation.

This operation is mainly performed in children. It was used in primary biliary cirrhosis, as well as in FPN, when there was no possibility of urgently obtaining a cadaveric liver. The disadvantage of the operation is also the lack of time for preoperative preparation of the donor, including psychological, and the preparation of autologous blood.

Heterotopic supplementary liver transplantation

In heterotopic transplantation, a healthy tissue of the donor liver is transplanted to the recipient, leaving his own liver. This operation can be performed with FPN, when there is hope for the regeneration of the liver, as well as for the treatment of certain metabolic defects.

Usually a reduced graft is used. The left share of the donor liver is removed, and the vessels of the right lobe are anastomosed with the portal vein and the aorta of the recipient. The donor's liver is hypertrophied, and the recipient's own liver is atrophied.

After restoration of the liver function of the patient, immunosuppressive therapy is stopped. By this time, the additional liver is atrophied and can be removed.

Xenotransplantation

Transplantation of the baboon liver was performed in the HBV- and HIV-positive patient with terminal stage of cirrhosis. Early results were good, but after 70 days the patient died from a combination of bacterial, viral and fungal infections. Such operations were not carried out in the future, which is due to the unresolved number of issues, including those related to the ethical side of the problem and the protection of animal rights.

Liver transplantation in pediatric practice

The average age of sick children is approximately 3 years; The transplantation was successfully performed in a child under 1 year of age. The main difficulty lies in the selection of a donor for children, which necessitates the use of graft fragments derived from the reduction or separation of adult donor liver.

The growth of children and the quality of life after liver transplantation do not suffer.

Small sizes of blood vessels and bile ducts cause technical difficulties. Before the operation, it is necessary to investigate the anatomical features of the patient with CT or, more preferably, magnetic resonance imaging. Thrombosis of the hepatic artery is observed in at least 17% of cases. Re-transplantation is often necessary. The frequency of biliary complications is also high.

In children under the age of 3 years, the annual survival rate is 75.5%. The kidney function may worsen after transplantation, which is due not only to the use of cyclosporine. Infectious complications, especially chicken pox, as well as diseases caused by the virus EBV, mycobacteria, fungi of the genus Candida and CMV often develop .

Immunodepression

Usually, multicomponent therapy is carried out, the choice of protocol is determined by the specific transplantation center. In most clinics use a combination of cyclosporine and corticosteroids.

Cyclosporine can be prescribed in the preoperative period orally. When it is impossible to take the drug inside it is administered intravenously. The administration of cyclosporine is combined with the intravenous administration of methylprednisolone.

After transplantation, cyclosporine is administered intravenously in fractional doses if oral administration of the drug is insufficient. In parallel, intravenously injected methylprednisolone, reducing its dose to 0.3 mg / kg per day by the end of the first week. If possible, therapy is continued by administering the drug orally. In other transplantation centers, cyclosporine is not used prior to transplantation, but azathioprine is prescribed together with methylprednisolone; Cyclosporine is started to enter, making sure the adequacy of kidney function. Long-term maintenance therapy is usually performed with cyclosporine at a dose of 5-10 mg / kg per day.

Side effects of cyclosporine include nephrotoxicity, but glomerular filtration usually stabilizes after a few months. Nephrotoxicity increases with the appointment of drugs such as aminoglycosides. Electrolyte disorders include hyperkalemia, hyperuricemia and a decrease in serum magnesium levels. Arterial hypertension, weight loss, hirsutism, gingival hypertrophy and diabetes mellitus are also possible. Lymphoproliferative diseases can be observed in the long term. Possible development of cholestasis. Neurotoxicity is manifested by mental disorders, seizures, tremors and headaches.

The concentration of cyclosporine and tacrolimus in the blood can change with the simultaneous administration of other medications.

Cyclosporine is an expensive drug; Due to the small breadth of the therapeutic effect, careful monitoring of treatment is necessary. It is necessary to determine its true concentration in the blood, at first often, and then regularly at regular intervals. The choice of dose is based on the nephrotoxicity of the drug. Side effects may require a dose reduction until cyclosporine is replaced with azathioprine.

Tacrolimus (FK506) is an antibiotic from the macrolide group, somewhat similar in structure to erythromycin. This preparation causes stronger inhibition of interleukin-2 (IL-2) synthesis and IL-2 receptor expression than cyclosporine. The drug was used to rescue patients with repeated crises of rejection of the transplanted liver. In its effect on the survival of recipients and the viability of transplants, it is comparable to cyclosporine. Tacrolimus less often causes episodes of acute and refractory to treatment of rejection and the need for corticosteroid therapy. However, the number of side effects that require discontinuation of treatment is greater than with cyclosporine. These include nephrotoxicity, diabetes mellitus, diarrhea, nausea and vomiting. Neurological complications (tremor and headache) with tacrolimus are more common than with cyclosporine. The main indication for the appointment of tacrolimus remains refractory rejection.

Interaction between cyclosporine (and tacrolimus) and other drugs

Increase the concentration of cyclosporine

• Erythromycin
• Ketoconazole
• Corticosteroids
• Metoclopramide
• Verapamil
• Diltiazem
• Tacrolimus

Reduce the concentration of cyclosporine

• Octreotide
• Phenobarbital
• Phenytoin
• Rifampicin
• Septrin (Bactrim)
• Omeprazole

Side effects of azathioprine - bone marrow depression, cholestasis, peliosis, perisinusoidal fibrosis and veno-occlusive disease.

Migration of cells and chimerism

Donor cells were found in recipients of the donor liver. This chimerism can affect the host's immune system, causing the development of tolerance to donor tissues. After 5 years, immunosuppressive therapy can be stopped without fear of developing graft rejection. Unfortunately, complete discontinuation is possible only in approximately 20% of cases, and a significant reduction in the dose of drugs - in 55% of recipients. In patients with liver transplantation performed in connection with autoimmune hepatitis, a decrease in the dose of immunosuppressants may lead to a relapse of the disease.

[1], [2], [3], [4], [5], [6], [7]