Donor selection and liver transplant surgery

The process of selecting donors for liver transplantation is standardized. However, the criteria for a “good” or “bad” liver vary from clinic to clinic. The growing need for liver transplantation has led to the use of donor organs that may have previously been considered unsuitable. However, there has been no significant increase in failures due to poor graft function.

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

Maintain adequate cardiovascular function, and perform artificial ventilation of the lungs to perform the respiratory function. Transplantation of the liver and other vital organs from donors with a contracting heart minimizes ischemia, which occurs at normal body temperature and significantly affects the outcome of the transplant.

The donor should not have other diseases, including diabetes and obesity. Histological examination should exclude fatty 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 ABO blood group may result in severe rejection reaction. Such a liver can be used in case of extreme necessity in emergency situations.

More difficult is the selection of a donor according to the HLA system. It has been proven that incompatibility of individual HLA class II antigens provides advantages, especially in preventing the development of vanishing bile duct syndrome.

The donor is tested for markers of viral hepatitis B and C, antibodies to CMV and HIV.

The details of the donor and recipient surgery are discussed in many papers. After the liver is isolated, it is cooled by injecting Ringer's solution through the splenic vein and additionally 1000 ml of the University of Wisconsin solution through the aorta and portal vein. A cannula inserted into the distal end of the inferior vena cava provides venous outflow. After excision, the cooled liver is additionally washed through the hepatic artery and portal vein with 1000 ml of the University of Wisconsin solution and stored in this solution in a plastic bag on ice in a portable refrigerator. This standard procedure has increased the storage time of the donor liver to 11-20 hours, made the recipient surgery "semi-planned" and feasible at a more convenient time. The same surgeon can perform the operations on the donor and recipient. Further improvements in organ preservation include the use of an automatic perfusion device after the liver is delivered to the transplant center. Graft viability can be assessed using nuclear magnetic resonance.

When selecting a donor liver, it is necessary that it matches the recipient's anatomical features in size and shape, if possible. The donor liver should not be larger and, if possible, should not be smaller than the recipient's. Sometimes a small liver is implanted in a large recipient. The donor liver increases in volume at a rate of approximately 70 ml per day until it reaches a size that matches the recipient's body weight, age, and sex.

Surgery on the recipient

The average duration of liver transplantation is 7.6 hours (4-15 hours). On average, 17 (2-220) units of red blood cell mass are transfused. The apparatus used to return red blood cells allows for the preservation of approximately one third of the volume of blood flowing into the abdominal cavity. The blood is aspirated and the red blood cells are injected into the patient after repeated washing and resuspension.

The anatomical structures of the liver gates, the vena cava above and below the liver are isolated. The isolated vessels are clamped, crossed, and then the liver is removed.

During the implantation of the donor liver, the blood flow in the splenic and vena cava systems must be interrupted. In the non-invasive period, venovenous shunting with a pump prevents blood deposition in the lower half of the body and edema of the abdominal organs. Cannulas are inserted into the inferior vena cava (through the femoral vein) and portal vein, and blood flows out into the subclavian vein.

Venovenous bypass reduces bleeding, increases the permissible operating time and makes it easier to perform.

All vascular anastomoses are completed before blood flow in the implanted liver is restored. Portal vein thrombosis must be excluded. Hepatic artery anomalies are common, and donor vascular grafts should be used for its reconstruction.

Anastomoses are usually performed in the following order: suprahepatic vena cava, infrahepatic vena cava, portal vein, hepatic artery, bile ducts. Biliary reconstruction is usually performed by performing a choledochocholedochoastomosis on a T-shaped drain. If the recipient has a diseased or absent bile duct, an end-to-side choledochojejunostomy is performed with the Roux-en-Y loop of jejunum. Before suturing the abdominal cavity, the surgeon usually waits approximately 1 hour to identify and eliminate any remaining sources of bleeding.

Liver transplantation (reduced or divided liver)

Because of the difficulty in obtaining small donor organs, a partial adult donor liver has come to be used for pediatric transplants. This method produces two viable grafts from a single donor organ, although usually only the left lobe or left lateral segment is used. The recipient to donor body weight ratio should be approximately 3:4. In 75% of pediatric liver transplants, a reduced adult donor organ is used.

The results are not as satisfactory as with whole organ transplantation (one-year survival rates are 75% and 85%, respectively). There are a large number of complications, including increased blood loss during surgery and inadequate blood supply to the graft due to portal vein hypoplasia. Graft loss and biliary complications are more common in children than in adults.

Liver transplant 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 donors are blood relatives of the patient who must give voluntary informed consent for the operation. This allows a transplant to be obtained in the absence of a cadaveric donor organ. This operation is performed on recipients with terminal liver disease or in countries where cadaveric organ transplantation is prohibited. With a high level of surgical technique and anesthetic care, as well as intensive care, the risk to the donor is less than 1%. The hospitalization period lasts on average 11 days, and blood loss is only 200-300 ml. Rarely, the donor may develop complications during and after the operation, such as damage to the bile ducts and spleen or abscess formation.

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

Heterotopic accessory liver transplantation

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

A reduced graft is usually used. The left lobe of the donor liver is removed, and the vessels of the right lobe are anastomosed with the recipient's portal vein and aorta. The donor liver hypertrophies, and the recipient's own liver undergoes atrophy.

Once the patient's liver function has been restored, immunosuppressive therapy is discontinued. By this time, the additional liver has atrophied and can be removed.

Xenotransplantation

A baboon liver transplant was performed on an HBV- and HIV-positive patient with terminal cirrhosis. Early results were good, but the patient died 70 days later from a combination of bacterial, viral and fungal infections. Similar operations have not been performed in the future, due to a number of unresolved 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 affected children is approximately 3 years; transplantation has been successfully performed in a child under 1 year of age. The main difficulty lies in selecting a donor for children, which necessitates the use of transplant fragments obtained by reducing or dividing an adult donor liver.

Children's growth and quality of life are not affected after liver transplantation.

The small size of the vessels and bile ducts causes technical difficulties. Before surgery, it is necessary to examine the patient's anatomical features using CT or, preferably, magnetic resonance imaging. Hepatic artery thrombosis occurs in at least 17% of cases. Retransplantations are often necessary. The incidence of biliary complications is also high.

In children under 3 years of age, the one-year survival rate is 75.5%. Kidney function may deteriorate after transplantation, which is not only due to the use of cyclosporine. Infectious complications often develop, especially chickenpox, as well as diseases caused by the EBV virus, mycobacteria, Candida fungi and CMV.

Immunosuppression

Multicomponent therapy is usually used, the choice of protocol being determined by the specific transplant center. Most clinics use a combination of cyclosporine and corticosteroids.

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

After transplantation, cyclosporine is given intravenously in divided doses if oral administration is insufficient. Methylprednisolone is given intravenously at the same time, tapering to 0.3 mg/kg/day by the end of the first week. If possible, therapy is continued orally. Other transplant centers do not use cyclosporine before transplantation but use azathioprine with methylprednisolone; cyclosporine is started after renal function is adequate. Long-term maintenance therapy is usually given cyclosporine at a dose of 5-10 mg/kg/day.

Side effects of cyclosporine include nephrotoxicity, but glomerular filtration usually stabilizes after several months. Nephrotoxicity is increased by drugs such as aminoglycosides. Electrolyte disturbances include hyperkalemia, hyperuricemia, and decreased serum magnesium levels. Hypertension, weight loss, hirsutism, gingival hypertrophy, and diabetes mellitus may also occur. Lymphomaproliferative disorders may occur in the long term. Cholestasis may develop. Neurotoxicity includes mental disorders, seizures, tremors, and headache.

The concentration of cyclosporine and tacrolimus in the blood may change when taken simultaneously with other drugs.

Cyclosporine is an expensive drug; its narrow therapeutic range requires careful monitoring of treatment. Its true blood concentration should be determined, frequently at first and then regularly at certain intervals. The dose is selected based on the drug's nephrotoxicity. Side effects may require a dose reduction, even to the point of replacing cyclosporine with azathioprine.

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

Interactions between cyclosporine (and tacrolimus) and other drugs

Increases the concentration of cyclosporine

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

Reduces the concentration of cyclosporine

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

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

Cell migration and chimerism

Donor cells have been identified in recipients of donor livers. This chimerism may affect the host immune system, causing tolerance to donor tissues. After 5 years, immunosuppressant therapy can be discontinued without fear of graft rejection. Unfortunately, complete discontinuation is possible only in approximately 20% of cases, and a significant reduction in drug dosage is possible in 55% of recipients. In patients who have had liver transplantation due to autoimmune hepatitis, a relapse of the disease may occur when the immunosuppressant dosage is reduced.

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