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.

 

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.   Donor liver from adult cut down for insertion into child recipient       Liver transplantation Top Liver transplantation Pancreatic 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 peritonitisabdominal pain (a late sign) Bleeding oesophageal or gastric varices Low albumin concentration Raised prothrombin time

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.

View larger version (40K): [in this window] [in a new window]   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.

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.

View larger version (29K): [in this window] [in a new window]   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.

Potential Therapy Reported for Children, Adults with End-Stage Liver Disease

By Carrie Wingate, Ph.D.

Researchers from Johns Hopkins in Baltimore recently reported findings that administration of a single chemical, methionine sulfoximine (MSO), to rats protected them from the effects of hyperammonemia, or excessive levels of ammonia in the blood. These findings are significant for human patients with liver disease, because in its final stages the condition leads to swelling of a type of brain cells called astrocytes, often leading to coma and death.

As the liver begins to fail, it can no longer process ammonia, which is a normally produced by the body as a by-product of other processes. The resulting hyperammonemia causes the formation of glutamine. Experimental evidence suggests that astrocytes begin to swell when glutamine accumulates in them and then attracts water as well. This swelling (encephalopathy) puts pressure on the brain and interrupts its normal functions.

MSO is known to prevent the formation of glutamine. In the animal study, the researchers pretreated rats with MSO and then induced hyperammonemia. When compared to rats that had not been treated first with MSO, the treated rats showed no swelling in their astrocytes or in their brains in general, and none of the animals showed any signs of brain damage.

The researchers hope to begin clinical trials of MSO in humans within a year.

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