LIVER TRANSPLANTATION

In 2002, 5329 liver transplantations were performed in the United States, including an increasing number of living liver donors. In the same period, 1132 cadaveric liver transplantations were documented by Eurotransplant, which covers six central European states. ^h As of spring 2003, 17,221 patients were on the waiting list for liver transplantation in the United States; approximately 1640 patients died in 2002 while awaiting liver transplantation. Nationwide, the 3-year survival rate after transplantation is over 75%.^[156] This rate underscores the fact that liver transplantation should not be considered experimental and is indeed the treatment of choice for eligible patients with end-stage liver disease. The growing discrepancy between organ supply and recipients on the waiting list has made finding alternatives to cadaveric liver transplantation of paramount importance. This discrepancy may become greater in view of the fact that cirrhosis will develop in 25% to 30% of the more than 4 million Americans with hepatitis C. ^{[157] [158]} Recurrent disease, especially with hepatitis C, will necessitate retransplantation in the years to come and further aggravate the acute organ shortage problem.^[159] The challenge of meeting organ shortages may be overcome if donor liver allocation is optimized and the donor pool can be increased with new approaches such as the use of living liver donors or suboptimal donors.

2246

Combined liver-kidney transplantation is performed infrequently, with only 69 performed in the United States in 1999. Renal disease in the setting of cirrhosis can be due to primary renal disease, hepatorenal syndrome, and acute tubular necrosis.^[160] Considerable controversy exists with regard to patient selection for this procedure because of the organ shortage and the possibility of inferior patient and graft survival when compared with single-organ transplantation. Hence, it is advocated that patients be highly selected and that hemodynamically stable patients with primary disease in both organs be preferred. ^[160]

Organ Matching and Allocation

The ABO blood group system is the primary immunologic barrier to transplantation,^[161] and this classification system is the most important for liver transplantation. The four ABO groups are not proportionally distributed among cadaveric donors and possible recipient candidates. Hence, the matching strategy between donor and possible recipient is crucial in liver allocation. Donor and recipient ABO blood type matching can be classified as follows: identical (e.g., A to A), compatible (e.g., O to A), and incompatible (e.g., A to O).^[162] In general, identical matching is preferred because patient and graft survival is superior with compatible organs. However, in select cases such as acute hepatic failure or acute deterioration of chronic liver disease, even incompatible organs are transplanted. Graft survival is poorer in patients receiving incompatible organs than in those receiving identical matching. However, acceptable patient survival may be achieved by retransplantation.

The organ allocation policy varies between countries. In the United States, cadaveric donor livers are allocated to patients who are registered with a national registry. In contrast, several European countries allocate donor livers primarily to transplant centers. These centers subsequently identify a suitable recipient candidate. Regardless of the respective organ allocation policy, recipient candidates have to be well screened regarding their eligibility for liver transplantation.

The number of diseases amenable to treatment with liver transplantation has steadily increased over the last few years. The single most important cause of end-stage liver disease is chronic hepatitis C, which is responsible for close to 40% of all liver transplantations. Causes of chronic disease in adults can be classified as follows: (1) noncholestatic (e.g., alcohol; hepatitis A, B, C), (2) cholestatic (e.g., primary biliary cirrhosis, primary sclerosing cholangitis), (3) metabolic disease (e.g., Wilson's disease), and (4) selected cases of hepatocellular carcinoma often associated with hepatitis B or C. Fulminant hepatic failure can be drug induced (e.g., acetaminophen overdose, idiosyncratic), caused by the ingestion of poisonous mushrooms or herbs, and secondary to acute viral hepatitis.^{[163] [164]}

Reasons to deny transplantation may vary from center to center. Liver transplantation is an extremely stressful procedure for patients. Significant CAD, cardiac dysfunction, and moderate to severe pulmonary hypertension are considered contraindications to liver transplantation. Uncontrolled infection or sepsis excludes a patient from transplantation as well. However, a positive HIV test, without evidence of acquired immunodeficiency syndrome, is no longer a contraindication. Recent case series have reported good results in HIV-infected patients undergoing liver or kidney transplantation.^[1] Advanced malignant hepatic disease or metastatic disease is in general considered to be a contraindication, as is uncontrolled and markedly documented elevated intracerebral pressure in the setting of fulminant hepatic failure. Psychosocial factors such as active alcohol abuse or the lack of a good social support system may prevent the patient from being a candidate for transplantation. Advanced age per se is not a reason to deny liver transplantation. Indeed, patients older than 65 years are increasingly undergoing transplantation.

In the past, the Child-Turcotte-Pugh (CTP) classification had been used widely as an index of disease severity for patients with end-stage liver disease. This classification, in conjunction with United Network for Organ Sharing (UNOS) status, was the determining factor for organ allocation in the United States until early 2002. However, because of shortcomings of CTP scores and subsequent limitations in organ allocation, the model for end-stage liver disease (MELD) has recently been introduced for adults in the United States.^{[165] [166]} This model resulted from a growing realization that the previous UNOS scoring system, which was based on the CTP score of liver disease severity plus the amount of time on a waiting list, did not always ensure that organs were allocated to the sickest patients with the greatest risk of mortality.

The MELD risk score is a mathematical formula based on the following factors:

1. Creatinine (for adult patients undergoing dialysis twice a week within the last week, the creatinine value will be automatically set to 4 mg/dL)
2. Bilirubin (mg/dL)
3. INR

Several adjustments in the new system have been introduced to make it as equitable as possible. Hepatocellular carcinoma confined to the liver can progress to inoperable lesions before manifesting changes in MELD criteria. UNOS has adopted the rule that patients with hepatocellular carcinoma be assigned a MELD score equivalent to the risk of death based on rapid disease progression. ^{[168] [169]} Finally, a peer review mechanism has been instituted, and the current classification is under constant review and adjustment. Early reports indicate that use of the MELD criteria has been shown to be better associated with 1-year patient survival in liver transplant recipients than the former UNOS status is.^[170]