Selection of patients for liver transplantation

Liver transplantation is indicated for patients with irreversible, progressive liver damage, when there are no alternative methods of treatment. The patient and his relatives should be aware of the complexity of the operation and be prepared for possible severe complications of the early postoperative period and for lifelong immunosuppressive therapy.

Selection of patients for surgery is particularly difficult due to a lack of donors. It is carried out by the Committee on the selection of patients for transplantation. Due to the severity of the condition, potential recipients are divided into low, moderate and high risk groups. Unfortunately, as the operation is expected, the patient's condition may deteriorate, which causes his transition to a higher risk group. In patients belonging to the group of low risk (outpatient), the results of treatment are much better, and its cost is lower than in high-risk patients who require intensive therapy during the waiting process.

In the US, the number of patients who need liver transplantation is increasing, but the number of donors varies insignificantly. The number of patients included in the waiting list of liver transplantation now exceeds the number of operations performed during the year. Patients at low risk can wait for the donor organ for 6-12 months. A patient with fulminant hepatic insufficiency (FPN) can wait for him only 4 days. The patients with the rare blood groups AB (III) and AB (IV), who are rare in the ABO system, are the longest remaining in the queue. A suitable donor for children can be found extremely rarely, which contributed to the development of the method of transplantation of the divided liver.

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

Potential recipients for liver transplantation

In Europe, absolute indications for liver transplantation are being revised. The main indication for the operation is cirrhosis, including primary biliary cirrhosis (PBC). More often began to operate patients with acute and subacute liver failure and atresia of the biliary tract, while in patients with liver cancer transplantation is performed less often.

Cirrhosis of the liver

The question of the possibility of performing liver transplantation should be considered in all patients with terminal stage of cirrhosis. It is difficult to establish optimal terms for the operation. In patients who are in the dying state, the chances of success are minimal, and patients who can lead a relatively normal lifestyle for a long time, surgery is not needed.

Indications for the operation are an increase in prothrombin time (PV) by more than 5 seconds, a decrease in the albumin level of less than 30 g / l and resistant to ascites therapy. The indication is bleeding from varicose-dilated esophagus veins in the absence of the effect of conservative therapy, including sclerotherapy. The cost of liver transplantation does not significantly exceed the cost of prolonged conservative and surgical treatment of complications such as bleeding, coma and ascites.

The operation in these patients is associated with a high risk due to disorders in the blood clotting system and the presence of portal hypertension, which leads to large blood loss. With cirrhosis of the liver, the operation is technically more complicated, especially when the liver is small and difficult to remove. Survival in all forms of cirrhosis is almost the same.

[7], [8], [9]

Chronic autoimmune hepatitis

Liver transplantation is performed at the stage of cirrhosis, as well as with the expressed side effects of corticosteroid therapy, such as osteoporosis and recurrent infections. After transplantation, the liver disease does not recur (see Chapter 17).

Survival among 9966 patients with cirrhosis of the liver, acute liver failure and liver cancer (data from the European Liver Transplant Register, 1993)

Diagnosis	Annual survival rate,%	Two-year survival rate,%	Three-year survival rate,%
Cirrhosis of the liver	80	73	71
Acute liver failure	60	56	54
Liver cancer	64	42	36

Diseases in which there may be a need for liver transplantation

Cirrhosis

• Cryptogenic
• Autoimmune
• Hepatitis B (HBV-DNA-negative)
• Hepatitis D
• Hepatitis C
• Alcoholic

Cholestatic liver disease

• Primary biliary cirrhosis
• Atresia of the biliary tract
• Primary sclerosing cholangitis
• Secondary sclerosing cholangitis
• Graft versus host disease
• Chronic liver rejection
• Sarcoidosis of the liver with cholestasis syndrome
• Chronic drug reactions (rare)

Primary metabolic disorders

Fulminant liver failure

Malignant tumors

• Hepatocellular carcinoma
• Epithelioid hemangiendothelioma
• Hepatoblastoma

Other diseases

• Badda-Chiari Syndrome
• Syndrome of the small intestine

[10], [11], [12], [13], [14], [15],

Transplantation for chronic viral hepatitis

Liver transplantation performed for acute fulminant hepatitis (A, B, D, and E) is not accompanied by a reinfection of the graft due to a very low level of viremia. However, with chronic hepatitis, the graft is very often prone to re-infection.

Hepatitis B

The results of liver transplantation in patients with chronic hepatitis B are unsatisfactory, probably due to extrahepatic replication of the virus, especially in monocytes. The annual survival rate is 80%, but the 2-year survival rate is only 50-60%. Transplantation should be performed only when there is no HBV DNA and HBeAg in the serum. In HBV-positive patients, the course of the post-transplant period is usually severe, with a progressive course of the disease; In 2-3 years, cirrhosis of the liver or cirrhosis and cancer develop. When re-implantation, remission is even shorter and quickly replaced by relapse and liver failure.

In the posttransplant period, severe fibrosing cholestatic hepatitis with balloon dystrophy of the hepatic cells and matte-vitreous hepatocytes can develop . This may be due to the high expression of viral antigens in the cytoplasm on the background of immunodepression. HBV can sometimes give a cytopathic effect. Attempts to prevent reinfection of the graft by interferon therapy (IFN) have for the most part been unsuccessful. Prolonged use of immunoglobulin against HBV reduces the likelihood of recurrence of infection in HBV-DNA positive patients if it is administered at the non-negligible stage of the operation, then daily for a week, then monthly for 1 year and possibly longer. This is a very expensive method of prevention. The introduction of lamivudine before and after transplantation can prevent reinfection. Ganciclovir may reduce the replication of HBV. In the transplanted liver, hepatocellular carcinoma can develop.

Hepatitis D

After liver transplantation in hepatitis D, transplant infection is almost always observed. In the transplanted liver, HDV-RNA and HDAg can be detected, and in the serum - HDV-RNA. Hepatitis develops only with co-infection or superinfection with HBV.

HBV is suppressed by HDV, and infection with HDV can reduce the incidence of hepatitis B relapse. In general, survival after liver transplantation in patients infected with HDV is high. The annual survival rate is 76%, and the two-year survival rate is 71%.

Hepatitis C

The terminal stage of hepatitis C increasingly serves as an indication for liver transplantation; At present, in a third of patients, the operation is performed precisely in connection with this condition.

Virtually all patients after transplantation re-infection of the donor organ. The source of reinfection is the host organism, since the virus genotype before and after transplantation is similar. Factors influencing the frequency of relapses include genotype 1b. The disease can be transmitted from an anti-HCV-positive donor. Currently, this route of infection is observed less frequently in connection with the screening of donors for HCV. Despite massive blood transfusion, the likelihood of transfusion of HCV-positive blood and the development of hepatitis C has not increased.

Annual, two- and three-year survival of patients with a good function of transplants is high and in patients with cirrhosis of the liver are respectively 94, 89 and 87%.

After transplantation, even in the absence of histological signs of hepatitis, there is a 10-fold increase in the level of HCV-RNA in the serum. More often, the activity of the process depends on the amount of corticosteroid and other chemotherapeutic drugs administered.

Reinfection is more often observed after multiple episodes of rejection.

Hepatitis of the transplant has a different severity. Typically, a mild course and high survival are characteristic. However, longer follow-up indicates an increase in the number of patients who develop chronic hepatitis and cirrhosis. Persistence of HCV can cause severe damage to the transplant, especially with the genotype of the lb virus.

Interferon treatment gives only a temporary effect and can increase the frequency of graft rejection. Combined treatment with interferon and ribavirin seems more effective; the histological picture of liver tissue improves and the frequency of rejection of the donor organ decreases.

Neonatal hepatitis

This disease of unknown etiology is accompanied by jaundice, the development of giant cell hepatitis and in rare cases liver failure, requiring liver transplantation, which leads to a cure.

Alcoholic liver disease

In Western countries, these patients constitute the majority among those who need liver transplantation.

[16], [17], [18], [19], [20]

Cholestatic liver disease

The terminal stage of diseases of the biliary tract, which usually proceeds with the lesion of small intrahepatic bile ducts, is a favorable indication for liver transplantation. The function of hepatocytes is usually maintained for a long time, and it is easy to choose the optimal time for the operation. In all patients in the liver, there are signs of widespread biliary cirrhosis, often in combination with the disappearance of bile ducts (the syndrome of disappearance of the bile ducts).

[21], [22], [23], [24], [25], [26], [27],

Primary biliary cirrhosis

The annual survival rate after liver transplantation exceeds 75%. Observation is described when, in connection with primary biliary cirrhosis and primary pulmonary hypertension, three organs (liver, lung and heart) were transplanted with a good result for 7 years.

Atresia of extrahepatic bile ducts

This disease is an indication for liver transplantation in children in 35 to 67% of cases. The results of the operation are good, and with a high survival rate, normal physical and mental development is observed.

According to researchers from Pittsburgh, the follow-up period for 12 out of 20 children after liver transplantation was from 1 to 56 months, with 19% of them requiring re-transplantation and 37% in various reconstructive surgeries. According to another study, in a group of 36 children, whose mean age at the time of liver transplantation was 30 months, the 3-year survival rate was 75%.

The previous operation of Kasai complicates the implementation of transplantation and increases the number of complications.

[28], [29], [30], [31], [32], [33], [34], [35]

Alajil Syndrome

Liver transplantation is performed only in cases of severe disease. Concomitant cardiopulmonary disease can be a cause of death, so a thorough preoperative examination is necessary.

[36], [37], [38], [39], [40], [41], [42], [43]

Primary sclerosing cholangitis

Sepsis and previous surgical interventions on the bile ducts make it difficult to perform liver transplantation. Nevertheless, the results of transplantation are good, the annual survival rate is 70%, and the 5-year survival rate is 57%. Cholangiocarcinoma is a complication that significantly reduces life expectancy. The most common cause of death is colon cancer.

Histiocytosis, caused by the proliferation of Langerhans cells, accounts for 15-39% of cases of sclerosing cholangitis. The results of liver transplantation with this disease turned out to be good.

Other cholestatic diseases in the terminal stage

The transplantation was performed to the bone marrow recipient, who developed cirrhosis due to graft-versus-host disease (GVHD). Other rare indications for surgery include sarcoidosis of the liver with cholestasis syndrome and chronic drug reactions (for example, the toxic effect of aminazine).

Primary metabolic disorders

The transplanted liver retains its inherent metabolic activity. In connection with this, liver transplantation is performed in patients with liver function defects, leading to congenital metabolic disorders. In patients suffering from these liver diseases, transplantation gives good results. When selecting patients, take into account the prognosis of the disease and the likelihood of developing in the long-term primary liver tumors.

Indications for liver transplantation in metabolic disorders:

1. terminal stage of liver disease or precancerous conditions,
2. significant extrahepatic manifestations.

The overall survival rate for the observation period of more than 5.5 years is 85.9%.

Insufficiency of alpha1-antitrypsin

This is the most common metabolic disorder, which is an indication for liver transplantation. Severe liver damage is observed only in a small number of patients, but the large-nodular cirrhosis develops in about 15% before reaching the age of 20 years. Complication is hepatocellular carcinoma. After liver transplantation, the level of a1-antitrypsin in the plasma is normalized and lung damage is stabilized. Severe changes in the lungs are a contraindication to surgery, if simultaneously with liver transplantation there is no plan to transplant the lungs.

Wilson's disease

Liver transplantation should be performed in patients with clinical signs of fulminant hepatitis, in young patients with severe decompensated liver cirrhosis and the absence of the effect of a 3-month adequate therapy with penicillamine, as well as in penicillamine-treated patients in the event of severe decompensation after discontinuation of the drug. The annual survival rate after liver transplantation is approximately 68%. The exchange of copper is normalized.

Neurologic manifestations are resolved with different frequency

Liver transplantation in metabolic disorders

End-stage liver disease or precancerous conditions

• Insufficiency of a1-antitrypsin
• Wilson's disease
• Tyrosinemia
• Galactosemia
• Diseases of accumulation of glycogen
• Protoporphyria
• Hemochromatosis neonatal
• beta-thalassemia
• Cystic Fibrosis
• The disease of Byler

Significant extrahepatic disorders

• Primary type I oxalaturia
• Homozygous hypercholesterolemia
• The Kriegler-Nayar Syndrome
• Primary disorders in the blood coagulation system (factors VIII, IX, protein C)
• Defects of the urea synthesis cycle
• Defects in the mitochondrial respiratory chain
• Primary familial amyloidosis

Diseases of accumulation of glycogen

Liver transplantation is successfully performed with glycogenases of types I and IV; while patients live to an adult status.

[44], [45], [46], [47], [48], [49]

Galactosemia

A small number of patients with a late diagnosed disease have progressive development of cirrhosis at childhood and young age. Such a patient shows liver transplantation.

Protoporphyria

This disease can lead to the terminal stage of cirrhosis, which is an indication for liver transplantation. In the postoperative period, a high level of protoporphyrin is retained in erythrocytes and in feces, i.e. The disease is not cured.

Tyrosinemia

Liver transplantation is a radical method of treatment, it should be performed in the early stages of the disease, before the development of hepatocellular carcinoma.

Neonatal hemochromatosis

Neonatal hemochromatosis can quickly lead to death. He is the manifestation of several diseases. The results of transplantation are ambiguous.

Beta-thalassemia

There is a report on combined heart and liver transplantation in an adult patient with homozygous beta-thalassemia in the terminal stage of organ failure caused by iron overload.

[50], [51], [52], [53], [54], [55],

Cystic Fibrosis

Liver transplantation is indicated with a predominant liver injury. Complications may be an infection caused by Pseudomonas spp. and Aspergillus spp. It is possible to improve lung function after transplantation.

[56], [57], [58], [59], [60], [61], [62]

The disease of Byler

This family disease, which occurs with intrahepatic cholestasis, leads to death from cirrhosis or heart failure. Liver transplantation, performed with cirrhosis, leads to a normalization of a lower concentration of apolipoprotein A1 in the serum.

Oxaluria

Primary type I oxalaturia, caused by a deficiency of the enzyme alaninglioxalate aminotransferase contained in peroxisomes, is corrected by simultaneous liver and kidney transplantation. The function of the heart is restored. Perhaps liver transplantation should be performed before the development of kidney damage.

Homozygous hypercholesterolemia

Liver transplantation leads to a decrease in serum lipid levels by 80%. Usually it is also necessary to perform a heart transplant or a coronary bypass.

The Kriegler-Nayar Syndrome

Liver transplantation is indicated for the prevention of neurological complications, when the serum bilirubin level is very high and not controlled by phototherapy.

Primary disorders in the blood clotting system

Liver transplantation is performed at terminal stages of cirrhosis, which was the outcome of viral hepatitis B or C. As a result, the normal level in the blood of factors VIII and IX is maintained and haemophilia A is healed. Deficiency of protein C is corrected.

Deficiency of urea synthesis cycle enzymes

Transplantation was performed with ornithine carbamoyltransferase deficiency, since urea synthesis enzymes are localized primarily in the liver. It is not easy to make a decision about the need for liver transplantation, since in some diseases associated with a violation of the urea synthesis cycle, a normal quality of life remains.

[63], [64], [65], [66], [67], [68]

Defects in the mitochondrial respiratory chain

These defects are at the heart of liver disease in newborns, manifested by hypoglycemia and hyperlactacidemia arising after ingestion. Liver transplantation led to the cure of such children.

[69], [70], [71], [72], [73], [74], [75], [76]

Primary familial amyloidosis

Liver transplantation is performed with incurable polyneuropathy. The degree of improvement in neurologic symptoms after the operation is different.

Fulminant liver failure

Indications for liver transplantation are fulminant viral hepatitis, Wilson's disease, acute fatty liver of pregnant women, drug overdose (for example, paracetamol) and drug-induced hepatitis (for example, caused by taking isoniazid and rifampicin).

Malignant tumors

The results of transplantation in patients with malignant liver tumors are poor, despite careful preoperative exclusion of extrahepatic tumor spread. In patients with cancer, operational mortality is low, but survival in the long term is the worst. Usually the cause of death is carcinomatosis. The tumor recurs in 60% of cases, which may be due to the use of immunosuppressants in order to prevent rejection.

Perioperative survival is 76%, but the annual survival rate is only 50%, and the 2-year survival is 31%. Regardless of the type of tumor for which liver transplantation was performed, the 5-year survival rate is 20.4%. Such results justify the implementation of transplantation.

Hepatocellular carcinoma

The size of the tumor should not exceed 5 cm. In the case of multifocal lesions, transplantation is performed in the presence of up to three tumor sites with a size of not more than 3 cm. By the time of transplantation, an important role is played by laparoscopy, which specifies the stage of the disease [118]. The presence of even a microscopic invasion of the vessels with a tumor increases the frequency of relapses and lethality. Preoperative chemotherapy or chemoembolization can delay the occurrence of relapse.

Survival in 2 years is 50%, while for diseases not related to malignant tumors, it is 83%. In this connection, the question arises whether transplantation of the donor liver is justified in patients with malignant tumors.

Transplantation may be preferable to resection with the occasional detection of small tumors in a patient with compensated cirrhosis of the liver.

Fibrolamellar carcinoma

The tumor is localized in the liver, and cirrhosis is absent. These patients are the most suitable "candidates" for transplantation among all patients with malignant liver tumors.

[77], [78], [79], [80], [81], [82], [83]

Epithelioid hemangiendothelioma

This tumor is represented by multiple focal lesions of both lobes of the liver, developing against the background of unchanged parenchyma. The course of the disease is unpredictable, and the probability of recurrence is 50%. The presence of metastases is not a contraindication to surgery and does not correlate survival. Liver transplantation can be successful.

[84], [85], [86], [87]

Hepatoblastoma

As a result of transplantation, 50% of patients live for 24-70 months. Poor prognostic signs are microscopic invasion of vessels and anaplasia of epithelium with extrahepatic dissemination.

Liver apodoma

Transplantation is sometimes performed as a palliative intervention even in the presence of secondary tumor lesions.

Transplantation of the complex of abdominal organs with malignant tumors in the right upper quadrant of the abdomen

Most of the organs originating from the embryonic anterior gut, including the liver, duodenum, pancreas, stomach and small intestine, are removed. Due to the use of powerful immunosuppressants, donor lymphoreticular cells circulate without causing clinical signs of GVHD and become intrinsic to the recipient; thus preventing rejection. Transplantation of a complex of organs is hardly justified, since patients usually die from tumor recurrence.

Cholangiocarcinoma

The results of transplantation with this disease are unsatisfactory, since the tumor usually recurs, and the life expectancy does not reach 1 year.

[88], [89], [90],

Badda-Chiari Syndrome

Despite the cases of successful liver transplantation, recurrence of thrombosis is high, especially in the Budd Chiari syndrome, which developed as a result of myeloproliferative disease.

[91], [92], [93]

Syndrome of the small intestine

Complex transplantation of the small intestine and liver is performed by patients with short bowel syndrome with secondary hepatic impairment.

Liver transplantation is also indicated in cystic fibrosis with concomitant liver cirrhosis and with Niemann-Pick disease in adults.