Starzl first attempted liver transplantation in 1963, and by 1967 had obtained prolonged survival. The first liver transplant performed outside the USA was undertaken in Cambridge by Caine in 1968. Throughout the 1970s liver transplantation remained a hazardous procedure that frequently failed, but the introduction of a number of changes led to improved results. These included improved immunosuppression, in the form of cyclosporin, together with improved patient selection and refinements in organ preservation and attention to technical aspects of the transplant operation. Liver transplantation is now a routine operation in specialist centres.
Indications and patient selection
The indications for liver transplantation fall into four groups:
• chronic cirrhosis;
• acute fulminant liver failure;
• metabolic liver disease;
• primary hepatic malignancy.
The most common indication for transplantation is chronic liver failure. In adults the causes include primary biliary cirrhosis, viral liver disease, alcoholic liver disease and sclerosing cholangitis. In children, who account for around 10—15 per cent of all liver transplants, biliary atresia is the most common indication for transplantation. Acute fulminant liver failure requiring transplantation on an urgent basis accounts for approximately 10 per cent of liver transplant activity and is viral or drug (e.g. paracetamol) induced. There is a variety of metabolic diseases for which transplantation offers the prospect of cure. These include Wilson’s disease, oxalosis and a1-antitrypsin deficiency. Hepatic malignancy is only occasionally treated by liver transplantation because of the high risk of tumour recurrence. Hepatomas, when they occur in a cirrhotic liver, may be best treated by transplantation and some centres consider transplantation for cholangiocarcinoma, although there is a high risk of recurrent disease.
Technique of liver transplantation
A transverse abdominal incision with a midline extension is made and the diseased liver mobilised . Because of portal hypertension the recipient hepatectomy is often the most difficult part of the operation, especially if there has been previous surgery in the region. The common bile duct is divided, as are the right and left hepatic arteries. The inferior vena cava is clamped and divided above and below the liver, and the portal vein is clamped and divided allowing the recipient liver to be removed. Occlusion of the vena cava and portal vein results in a reduction in cardiac output and may necessitate the use of veno-venous bypass. The bypass circuit delivers blood from the portal vein and inferior vena cava back to the heart via a cannula inserted into the axillary vein or the internal jugular veins. After placing the donor liver in position, the supra- and infrahepatic caval anastomoses are performed The portal vein and the hepatic arterial anastomosis are then completed and the graft is reperfused. Finally, biliary drainage is re-established, usually by a duct-to-duct anastomosis (without the use of a T-tube). It may be necessary, for example in recipients with biliary atresia or sclerosing cholangitis, to reconstruct the biliary drainage by a bile duct to Roux loop anastomosis. An alternative ‘piggyback’ technique of liver transplantation is sometimes preferred in which the diseased native liver is dissected from the intact inferior vena cava and the suprahepatic vena cava of the donor is anastomosed end-to-side to the anterior wall of the recipient cava.
Many patients undergoing liver transplantation are extremely ill and the surgery involved can be very technically demanding. Optimal perioperative management is crucial to a successful outcome and presents a major challenge. Blood loss during and after the transplant procedure can be very considerable and management of coagulopathy is particularly important. Coagulation is assessed repeatedly throughout the peritransplant period. Many centres use a thromboelastogram to supplement the information from standard coagulation screening. The thromboelastogram comprises an oscillating cuvette into which a small blood sample is placed and into which a piston suspended by a torsion wire is then lowered. As the sample clots, fibrin strands transmit elastic forces to the piston and are recorded to provide an index of coagulation.
Meticulous homeostasis during the transplant operation is important in order to minimise the risk of early haemorrhage. It may occasionally be necessary to pack the peritransplant area for 2—3 days to achieve adequate haemostasis when there is diffuse oozing despite correction of coagulopathy. Evacuation of extensive perihepatic haematoma may be required to avoid secondary infection.
Hepatic artery thrombosis may occur spontaneously or as a result of acute rejection, and is more common in paediatric recipients. It may present as a rise in serum transaminase levels, unexplained fever or bile leak. Doppler ultrasound or angiography are used to confirm the diagnosis and urgent retransplantation is usually required. Portal vein thrombosis presents more insidiously and does not usually require retransplantation.
Biliary leaks are now relatively uncommon and biliary stenosis is a more common problem. It usually occurs late after transplantation and is managed by endoscopic dilatation and stenting, and less often by surgical correction.
Paediatric liver transplantation
Until recently, the major factor limiting paediatric liver transplantation was the lack of suitably sized donor livers. However, as noted earlier, the development of techniques for using adult livers that have been reduced in size by cut-down techniques has greatly alleviated the problem. For small children, the lateral segment of the left lobe is often used but the entire left lobe or the right lobe may also be used in this way.
Outcome after liver transplantation
The outcome after liver transplantation depends on the underlying liver disease and the best results are seen in patients with chronic liver disease. Patients undergoing transplantation as a result of acute liver failure have a higher mortality in the early post-transplant period because of multiorgan failure, but those who make a satisfactory recovery have very good long-term liver allograft survival. Conversely, patients transplanted for tumour have a very good early outcome but ultimately fare much less well because of recurrent malignancy. Patients receiving a liver transplant following hepatitis B or hepatitis C infection often develop graft failure as a result of recurrent viral disease.
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