Liver transplantation has emerged from its status as an experimental procedure more than a decade ago to its current position as the preferred treatment for end-stage liver disease. Increasing numbers of patients on the waiting list and the traditionally small pool of donor organs have prompted the establishment of formal listing criteria to optimize organ utilization.

There are no age limits when considering patients for liver transplantation. The absence of significant disease in the heart, brain, lungs, and kidney would favor consideration for transplantation regardless of age. A patent portal or superior mesenteric vein is necessary for successful engraftment. If evidence of partial or complete thrombosis is apparent on initial imaging studies, then angiographic confirmation is recommended. Hepatopulmonary syndrome (hypoxemia related to cirrhosis) occurs occasionally and usually subsides following transplantation. Significant pulmonary hypertension, on the other hand, precludes transplantation since cardiac deterioration following engraftment inevitably occurs and is usually fatal. Patients who are HIV positive or who have psychiatric diseases such as depression and psychosis are not suitable candidates. Patients with a remote (greater than 5 years) history of malignancy in a nonhepatic site may be considered for liver transplantation.

The timing of liver transplantation in end-stage liver disease is not clearly established. Advanced cirrhosis is complicated by variceal hemorrhage, ascites, encephalopathy, hepatorenal syndrome, and hepatocellular carcinoma. A number of treatment options are available for the therapy of these complications. However, the referral of patients for transplantation after severe decompensation, i.e., in the face of severe malnutrition, aspiration pneumonia, ARDS, persistent gastrointestinal hemorrhage or renal failure, bodes a poor outcome.

In the United States, the most common indication (20-30%) for liver transplantation is cirrhosis due to chronic viral hepatitis. Although viral hepatitis B and C recur frequently in the transplanted liver, the administration of high doses of hepatitis B immune globulin at frequent established intervals following transplant has reduced the recurrence rates of hepatitis B significantly, improving both graft and patient survival. The administration of the nucleoside analogue, lamivudine, to patients prior to transplant is expected to reduce viral replication and promises to enhance this benefit. The progression to cirrhosis in about 10-20% of patients with hepatitis C permits consideration for transplantation in these patients. However, there are no strategies to prevent the recurrence of hepatitis C in the post-transplant period as exist for hepatitis B, and the majority of patients develop recurrent hepatitis C soon after transplantation. However, long-term survival is the rule in these patients although there may be a slow progression to cirrhosis.

Alcoholic liver disease accounts for about 20% of all liver transplants. Patients with substance abuse history may be considered for transplantation. Current recommendations are: abstinence for longer than 6 months, successful completion of a formally approved program for rehabilitation from substance abuse, and the existence of a favorable living environment after subjective evaluation by a psychiatric social worker.

Cirrhosis due to autoimmune, cryptogenic, cholestatic (biliary cirrhosis, primary sclerosing cholangitis, biliary atresia), metabolic, and genetic diseases comprise the remaining indications for liver transplantation.

For acute liver failure, regardless of etiology, liver transplantation is the treatment of choice, provided this can be achieved before the patient develops deep encephalopathy, irreversible brain edema, and herniation. Patients with early stage hepatocellular carcinoma can be successfully transplanted while those with more advanced disease are not usually considered candidates for liver transplantation unless they are first treated successfully under specific chemotherapy protocols.