General Contraindications to Liver Transplantations

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Some patients referred for liver transplantation can benefit more from a different therapy. There is also risk involved with pursuing another therapy that turns out to be ineffective and thus delays the referral for liver transplantation. In many cases, it makes sense to place the patient on the active transplant waiting list while closely observing the effects of other therapeutic interventions.

Special consideration should be given to the young infant who presents with liver failure. Some of the causes of liver failure in this age group can be treated with medical therapy. For instance, chelation and antioxidant therapy are now used to treat neonatal hemochromatosis. Albeit the rate of survival with medical therapy is only 30 to 40%, but that may be similar to survival after OLT in neonates.

Transplantation should be withheld if the candidate has a preexisting condition that will lead to a poor quality of life following transplantation. This applies particularly to the central nervous system (CNS). Congenital malformations or secondary injury to the brain (eg, intracranial hemorrhage or hyperammonemia) often lead to severely impaired children after transplantation. Furthermore, some systemic disorders cause hepatic injury and progressive CNS disease. Alpers' disease is characterized by primary degeneration of cerebral gray matter in association with liver disease and can present as fulminant hepatic failure in young children. Careful review of the patient's history reveals signs of progressive neurologic impairment, such as loss of developmental milestones and new-onset seizures in the weeks to months preceding their presentation with liver failure. Liver transplantation does not halt the cerebral degeneration, and transplanted patients subsequently die of neurologic complications despite good graft function. Every effort should be made to identify and specifically diagnose these types of disorders before liver transplantation to avoid futile therapy. It may not be possible to make reasonable predictions about neurologic outcome in some cases, such as the previously healthy child with fulminant hepatic failure and deep hepatic coma. Liver transplantation almost always reverses encephalopathy, but recovery from cerebral edema is often incomplete, and sometimes brain death follows successful transplantation.

Secondary organ failure has a negative effect on outcome after liver transplantation. For example, the development of intrapulmonary shunts, with or without pulmonary hypertension, can result in respiratory failure that may not recover. Severe pulmonary hypertension is associated with a high risk of operative death and is considered by most to be an absolute contraindication to transplantation. In less severely affected patients, there is no way to predict which patients will recover after liver transplantation. Rather, the presence of significant intrapulmonary shunting may be an indication for transplantation, but full recovery can be expected to require prolonged ventilatory support. The patient with functional renal insufficiency (hepatorenal syndrome) is managed by establishing access for renal dialysis before or during the liver transplant procedure. Renal function recovers after liver replacement, so oliguric renal failure need not be considered an indication for combined liver and kidney transplantation. Any systemic infection is a relative contraindication to liver transplantation. In some cases, however, there is no reasonable chance that the infectious complication can be adequately treated without transplantation, as in patients with biliary atresia and unremitting cholangitis and liver transplant recipients who have developed intrahepatic infection secondary to loss of arterial flow to their graft.

Acute viral hepatitis is not a contraindication to transplantation. Survival in this group is generally good, and recurrence of the infection in the graft is uncommon. However, liver transplantation should usually be deferred in patients with systemic viral infections. Simple upper respiratory infections can result in viral pneumonia with respiratory failure when patients are placed on immunosuppression. Our experience with a few children with respiratory syncytial virus and parainfluenza virus who died from overwhelming infection after liver transplantation serves to underline this caution. Transplantation should be delayed if possible until any acute viral infection, no matter how trivial, is resolved. The only exception to this is when there is an effective antiviral treatment available, such as varicella and cytomegalovirus.

A final contraindication to liver transplantation is disease that is expected to recur after therapy. Although the recurrence rate of chronic viral hepatitis is high, cirrhosis secondary to viral hepatitis is a common indication for liver transplantation. Studies in adults have shown that recurrence of hepatitis B and hepatitis C can be delayed or prevented by medical treatment after transplantation. There is much controversy regarding offering liver transplantation to human immunodeficiency virus (HIV)-positive patients. Some centers routinely perform transplantation in such patients, whereas others deny therapy on the assumption that the reduced length and quality of life posttransplantation cannot justify the therapy.

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