Clinical Review ABC of diseases of liver, pancreas, and biliary system

Transplantation of the liver and pancreas

BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7290.845 (Published 07 April 2001) Cite this as: BMJ 2001;322:845
  1. K R Prasad,
  2. J P A Lodge

    Liver transplantation is carried out for many chronic liver diseases and for fulminant hepatic failure. The United Kingdom has seven liver transplantation units, which perform 600–700 transplantations a year. Activity is limited by availability of donor organs, and there are around 200 patients waiting for a liver transplant at any one time. Transplantation of the pancreas is less well established. The pancreas is usually transplanted together with a kidney in patients with end stage diabetes mellitus and renal failure. Worldwide, around 1000 patients (mainly in the United States) receive a pancreatic transplant each year. Only 20–30 a year are transplanted in the United Kingdom.


    Embedded Image

    Donor liver from adult cut down for insertion into child recipient

    Liver transplantation

    Indications and contraindications

    Hepatocellular carcinoma complicates many chronic liver diseases, and a small tumour is not a contraindication to transplantaton because tumour recurrence is uncommon in these patients. However, most patients with large (>5 cm) or multiple hepatomas or most other types of cancer are not considered for transplantation as tumours recur rapidly. Patients with certain rare tumours, such as liver metastases from neuroendocrine disease and sarcomas, can do well for several years. Contraindications to liver transplantation include extrahepatic malignancy, severe cardiopulmonary disease, systemic sepsis, and an inability to comply with regular drug treatment.

    Common indications for liver transplantation

    • Primary biliary cirrhosis

    • Primary sclerosing cholangitis

    • Cryptogenic cirrhosis

    • Chronic active hepatitis (usually secondary to hepatitis B and C)

    • Alcoholic liver disease (after a period of abstinence)

    Timing and selection of patients for transplantation

    The preoperative status of the patient is one of the most important factors predicting the outcome after transplantation. Patients with chronic liver disease and signs of decompensation should be assessed for transplantation before they become critically ill. In certain diseases, such as primary biliary cirrhosis, quality of life issues may form the basis for indication for transplantation. For example, chronic lack of energy can be debilitating in patients with biliary cirrhosis.

    Signs of decompensation in chronic liver disease

    • Tiredness

    • Ascites

    • Encephalopathy

    • Peripheral oedema

    • Jaundice (not always a feature)

    • Spontaneous bacterial peritonitis—abdominal pain (a late sign)

    • Bleeding oesophageal or gastric varices

    • Low albumin concentration

    • Raised prothrombin time

    Acute liver failure and timing of transplantation

    Liver transplantation greatly improves the prognosis of patients with fulminant liver failure. In the United Kingdom paracetamol overdose is now the commonest cause of acute liver failure, followed by seronegative (non-A, non-B, non-C) hepatitis.

    Paracetamol overdose

    • Causes death by acute liver failure

    • Renal failure develops as a hepatorenal syndrome and by acute tubular necrosis but is usually recoverable

    • Early deaths usually result from raised intracranial pressure, and comatose patients require monitoring in an intensive care unit

    • Death in later stages can occur from multiorgan failure and systemic sepsis

    • If the patient survives without transplantation, the liver will recover without the development of cirrhosis

    The donor organ is usually procured as part of a multiorgan retrieval from a heart beating, brain dead patient

    The mortality from fulminant liver failure can be as high as 90%, whereas one year survival after urgent transplantation is often above 70%. In the United Kingdom, criteria developed at King's College Hospital are used for listing patients for “super urgent” transplantation. This scheme relies on cooperation between the liver transplantation centres to allow transplantation within 48 hours of listing whenever possible.

    Surgical procedure

    Before organs are removed an exploratory laparotomy is done on the donor to rule out any disease process (such as unexpected carcinoma) that may preclude organ donation. The major vessels are then dissected and blood flow controlled in preparation for hypothermic perfusion with a cold preservation solution. University of Wisconsin preservation solution is used most widely. It can preserve the liver adequately for about 13 hours, with acceptable results up to 24 hours.

    Figure1

    Implantation of liver transplant after hepatectomy

    Hepatectomy in the organ recipient is the most difficult part of the operation as the patient is at risk of developing a serious haemorrhage due to a combination of portal hypertension, defective clotting, and fibrinolysis. Improvements in surgical technique and anaesthesia have resulted in large reductions in blood loss, and the average requirement for transfusion is now four units of blood. At reimplantation, the suprahepatic and infrahepatic inferior vena cava and the portal vein are anastomosed and the organ is reperfused with blood. This is followed by reconstruction of the hepatic artery and bile duct.

    Postoperative management

    Patients are usually managed in an intensive care unit for the first 12–24 hours after surgery. Enteral feeding is restarted as early as possible, and liver function tests are done daily. Immunosuppressive protocols usually include a combination of cyclosporin or tacrolimus together with azathioprine or mycophenolate mofetil and prednisolone. The dose of steroids is rapidly tapered off, and they can often be stopped after two to three months. The doses of cyclosporin or tacrolimus are reduced gradually during the first year (during which pregnancy should be avoided) and continued at much lower levels for life.

    Side effects of immunosuppresive drugs

    Side effects of immunosuppresive drugs

    View this table:

    Acute rejection occurs in about half of patients, but this is easily treated in most cases with extra steroids or by altering the drug regimen. Despite routine use of prophylactic treatment against bacterial, viral, and fungal pathogens, infections remain a major cause of morbidity. The side effects of the drugs are usually well controlled before the patient leaves hospital about two weeks after surgery.

    At discharge, patients need to be familiarised with the drug regimen and side effects and educated about the warning signs of rejection and infection. Patients are usually followed up weekly for the first three months and then at gradually increasing intervals thereafter.

    Results

    The five year survival is 60-90%, depending on the primary disease and the clinical state of the patient before transplantation. The newer antiviral drugs plus the preoperative and postoperative adjuvant therapies for malignancies should lead to further improvements in survival. Although alcoholic liver disease remains a controversial indication for transplantation, carefully selected patients do well.

    After successful transplantation patients have a greatly improved lifestyle and are often able to return to work and normal social activities. However, some patients experience medical and social problems. Drug compliance is one of the biggest problems after all types of organ transplantation. Poor compliance leads to chronic rejection and loss of the graft.

    Figure2

    One year survival after first liver transplant according to primary disease, United Kingdom 1985-94

    An extensive network of support services is available to help liver transplant patients. These include the transplant team, referring physician, general practitioner, social services, and local liver patient support groups. Shared care protocols operate in most regions, with most patients cared for primarily by their general practitioner and a gastroenterologist at their local hospital. The mainstay of follow up is regular liver function tests to detect any dysfunction of the transplant. Regular discussion of concerns with the transplant team is essential, and many problems can be sorted out by telephone.

    Paediatric liver transplantation

    In children, the most common indication for liver transplantation is biliary atresia, often after failure to respond to a portoenterostomy. Most children who need a liver transplant are young (under 3 years) and small (<20 kg). Size matched donors are in short supply, and reduced size (”cut down”) and split (where one liver is split between two recipients) liver techniques have been used to overcome this problem. Donation of the left lobe of the liver by a living relative is also possible.

    The shortage of child liver donors has been partly resolved by using smaller sections of adult livers, usually the left lobe

    Pancreatic transplantation

    The goals of transplantation of the pancreas are to eliminate the morbidity associated with labile blood glucose concentrations, stabilise or improve secondary diabetic complications, and improve the quality of life of patients with diabetes mellitus by restoring normal glucose metabolism. The stabilisation of diabetic control, the avoidance of exogenous insulin, and the ability to return to a normal diet for the first time since childhood are indisputable benefits of this procedure.

    Types of pancreatic transplantation

    Types of pancreatic transplantation

    View this table:

    The selection of recipients for pancreatic transplantation is crucial. The magnitude of the surgery and need for long term immunosuppression means that whole organ transplantation is currently reserved for patients with end stage disease. Recipients are typically young (<50 years) with type 1 diabetes and end stage renal disease but without untreatable peripheral vascular or coronary artery disease. Simultaneous transplantation of the pancreas and kidney is the commonest procedure. Separate transplantation of the pancreas after kidney transplantation increases the chances of getting a good HLA matching for the kidney and allows a kidney to be donated by a living relative. The presence of immunosuppression at the time of implantation of the pancreas is also advantageous. The transplanted pancreas is usually placed in the pelvis and anastamosed to the iliac vessels, with the pancreatic duct anastomosed to the bladder or a loop of small bowel.

    Figure3

    Simultaneous transplantation of pancreas and kidney with bladder drainage

    First year mortality is 3-10% in large units, with most deaths due to overwhelming sepsis. Transplant survival is 86% for the kidney and 70% for the pancreas. Successful transplantation greatly improves quality of life, and most patients are fully rehabilitated. Glucose homoeostasis seems to be excellent after pancreatic transplantation. Patients can stop exogenous insulin treatment and have normal glycated haemoglobin concentrations and glucose tolerance test results within three months of transplantation.

    Summary points

    • Hepatitis C cirrhosis is the commonest worldwide indication for liver transplantation

    • Alcoholic liver disease remains a controversial indication for liver transplantation but carefully selected patients do well

    • Patients with chronic liver disease and signs of decompensation should be assessed for transplantation before they become critically ill

    • Drug compliance is an important problem, with poor compliance leading to chronic rejection and graft loss

    • Paracetamol overdose is the commonest cause of acute liver failure in the United Kingdom and accounts for 5% of all liver transplants in Britain

    • Pancreas transplantation is most commonly performed for patients with end stage diabetes mellitus and renal failure

    The long term effect on diabetic complications will not be known for several years, but recent results are encouraging. Evidence that diabetic nephropathy does not recur in the kidney transplant is accumulating, but there is no evidence for amelioration of established glomerular lesions in native kidneys. Improvements in autonomic and peripheral neuropathy have been documented. Further studies are needed to examine the potential for reducing the rate of progression of retinopathy and macrovascular disease.

    Isolated pancreatic islet transplantation

    A more logical approach is to attempt to prevent the development of the irreversible complications of diabetes by improving blood glucose metabolism at an early stage. Transplantation of pancreatic islet cells has been studied extensively as an alternative to whole organ grafting and has several theoretical and practical advantages. Pancreatic islets can be isolated by using collagenase digestion to separate the endocrine from the exocrine tissues and purified by density gradient separation. Some difficulties remain, particularly with the purification stage. The islets are injected into the recipient liver via the portal vein or by subcapsular injection into the kidney or spleen. Rejection of the islets remains a problem, and the success rates of this type of transplantation have been poor in the clinical setting.

    Acknowledgments

    The photo of donor liver was obtained from J L Martha/Science Photo Library.

    Footnotes

    • K R Prasad is senior transplant fellow and J P A Lodge is consultant hepatobiliary and transplant surgeon, St James Hospital, Leeds.

    • The ABC of diseases of liver, pancreas, and biliary system is edited by Ian Beckingham, consultant hepatobiliary and laparoscopic surgeon, department of surgery Queen's Medical Centre, Nottingham (Ian.Beckingham{at}nottingham.ac.uk). The series will be published as a book later this year.

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