Current Indications, Contraindications, Delisting Criteria, and Timing For Transplantation

Organ Allocation System

The organ allocation system has caused more controversy and discussion than any other in the field of LT. The earliest system was based on the Child-Turcotte-Pugh (CTP) score. The CTP score takes into account the presence of hepatic encephalopathy, ascites, serum bilirubin, albumin, and increase in prothrombin time above control values. From 1 to 3 points for each of the five parameters are assigned, and then a score is calculated with 5 to 6 points being class A, 7 to 9 points class B, and 10 to 15 points class C. CTP class A patients have compensated disease with better prognoses, and class C represents severely decompensated disease with poor prognosis. Before 2002 the CTP score was used to prioritize for the liver transplant waiting list, with listing using a status code (1, 2a, 2b, 3) based on a combination of CTP class (B versus C) and if the patient was at home, in the hospital, or in the intensive care unit. Because of the broad groups, priority was given within each group to patients who had been on the transplant list for a longer period, and waiting time became the major driver of transplant priority. It also allowed for a degree of subjectivity and claims of altering the data by overstating the degree of subjective variables (ascites, encephalopathy) to advocate for particular patients. It became clear that a different method of determining transplant priority was needed.

A more objective, laboratory-based measure of the risk for death on the waiting list was derived from a tool to assess the risk for death after transjugular intrahepatic portosystemic shunt procedures, the Model for End-Stage Liver Disease (MELD) score. This score is calculated from a logarithmic transformation of the serum bilirubin, international normalized ratio of prothrombin time, and serum creatinine. Though the values of MELD have no upper bound, for organ allocation purposes the minimum value is 1 for each value (to prevent negative logarithm values), for creatinine the maximum is capped at 4 (with a 4 given for hemodialysis), and the scale is capped at 40. This yields a MELD range from 6 to 40 for adults, with an open-ended scale for children called the Pediatric End-Stage Liver Disease model. The MELD score was validated to predict short-term mortality for patients with chronic liver disease and subsequently adopted by UNOS in 2002. Following the change to the MELD system, median waiting time was reduced, waiting list size decreased (6% reduction), new waiting list registration decreased (12% reduction between February 2002 and February 2003) with increased rates of transplantation (6% increase) as patients who were more gravely ill were prioritized. As a result, waiting list mortality was reduced without adversely affecting posttransplant survival.

One group of patients that takes precedence over those with the highest MELD scores is those with acute liver failure, including those with primary nonfunction of a transplanted liver. The need for rapid transplant in this group and its relative rarity (<10% of total transplants) has allowed these most critically ill patients to be better served in recent years with an allocation system that allows for acute liver failure patients to be listed above chronically ill patients.

Allocation of livers to patients with chronic liver disease is conducted slightly differently. Since February 2002, allocation of organs has been from the highest MELD to the lowest MELD. Through the MELD system, patients with the highest risk for short-term mortality are given priority. Waiting time becomes a secondary factor because waiting time accrued at prior lower MELD scores is not included and thus only the waiting time at the highest MELD score is used for ties. Thus the prioritization is now based on severity, rather than waiting time. Implementation of the MELD system led to the first reduction in liver transplant waiting list registrations in the history of LT, and the median waiting time to LT decreased. It was found that in patients with MELD scores of 14 or below, the mortality rate with LT was higher than that of patients with the same MELD score who had not undergone transplantation ( Fig. 8-1 ). Currently a MELD score higher than 15 is considered a valid indication for LT in patients with ESLD. At each liver center a detailed multidisciplinary evaluation is conducted to ensure that LT is both feasible and indicated.

There are limitations to the MELD system, and not all patients with ESLD are well served by the current system. Some have diseases that do not carry an immediate mortality risk or a risk that is not manifest by elevation in the international normalized ratio or bilirubin or creatinine levels (e.g., portal hypertension). Those with hepatocellular carcinoma (HCC) have a relatively well-preserved synthetic function and were initially not given priority in organ allocation, consequently suffering high dropout because of tumor progression and thus mortality on the waiting list. HCC became the most common of several accepted “MELD exceptions” to the standard allocation algorithm, which have been identified to be underserved by the MELD score allocation system and which receive “exception points” to rise higher on the list. These include HCC (and in some regions cholangiocarcinoma [CCA]), amyloidosis, hepatopulmonary syndrome, and recurrent cholangitis, which receive automatic increases with proper documentation. Other conditions, including refractory hepatic encephalopathy, portopulmonary hypertension, intractable pruritus, Budd-Chiari syndrome, cystic fibrosis, hereditary hemorrhagic telangiectasia, polycystic liver disease, primary hyperoxaluria, and small-for-size syndrome, can receive extra MELD points if approved by a regional review board.

Some studies have tried to improve the predictive accuracy of the current MELD system to address the populations that are underserved by the model. Values such as serum sodium (MELD-Na), age (integrated MELD), albumin, and ΔMELD, using a time-dependent analysis, have all been examined, but the standard MELD remains the model used at the present time. Other critiques of the MELD system are that it has increased the number of combined liver/kidney transplants and the transplants for HCC, increasing the waiting time and waiting list mortality for patients without HCC. Finally, though it addresses prioritization within each organ allocation unit, it has not significantly affected allocation and has not substantially reduced geographical differences in organ availability. A study of the impact of the MELD system in Switzerland showed that post MELD there was a lower mortality on the waiting list (386 versus 242 deaths per 1000 patient-years, P < .0001), increased posttransplant morbidity mainly because of renal failure (46% versus 13%, P < .0001), and a 55% increase in the cost of LT. The increase in cost is likely due to the transplantation of sicker patients who require more costly procedures and prolonged stays in the intensive care unit.

Data from the Scientific Registry of Transplant Recipients showed that liver transplants for candidates with low MELD scores (<15) were associated with a higher risk for death with the transplant than that of similar candidates who remained on the waiting list. This realization led to modifications of the allocation policy in 2005 under a rule called Share 15 . The previous process of offering donor livers to all candidates within the donation service area of the local organ procurement organization in descending order of MELD 6 to 40 was changed to allow for regional candidates with MELD scores above 15 outside the local area to receive offers before local candidates with MELD scores below 15.

The Evaluation

The evaluation process for LT seeks to define patients who will obtain the most benefit from transplantation, have the best chance for postoperative recovery and survival, and will value and take care of the precious resource (the organ graft) afforded to them. Referral is made once liver failure develops, ideally in a timely fashion to allow for a thorough assessment for candidacy. There are several basic questions that must be answered, including the following :

• 1.

  Is there an alternative treatment for the liver disease?

• 2.

  Can the patient survive the operation and postoperative period?

• 3.

  Are there other comorbid conditions that severely limit patient survival, making transplantation inappropriate?

• 4.

  Can the patient comply with the complex medical regimen required after transplantation?

• 5.

  Is the recurrence rate of the disease in the transplanted liver acceptable?

The process involves intense medical, surgical, psychiatric, social, and financial screening to identify those who may have contraindications to solid organ transplantation ( Table 8-1 ). Once the screening is completed, a committee, usually composed of hepatologists, transplant surgeons, transplant coordinators, psychiatrists, and social workers, comes together to determine who is appropriate for listing based on objective and subjective criteria. Once a patient is deemed to be an appropriate candidate for transplantation, he or she is placed on the national UNOS waiting list.

Management on the Waiting List

The transplant team must assist in the medical care of a patient who is listed for LT and awaiting an organ. This includes standard screening and surveillance procedures for patients with decompensated cirrhosis, including esophagogastroduodenoscopy screening for varices, primary or secondary prophylaxis against variceal bleeding, HCC screening, and treatment of complications of ESLD, including ascites, encephalopathy, gastrointestinal bleeding, and HCC. MELD scores are updated approximately every 3 months on average, or when clinical deterioration occurs.

As stated earlier, patients with MELD scores less than 15 do not have a survival benefit in the first year, and there is a larger survival benefit for each increase in the MELD score above 15. Other studies have shown the MELD score to be a relatively poor predictor of transplant outcomes in all except those with the highest 20% of MELD scores. There is no absolute MELD cutoff for transplant futility. For living donor recipients, an analysis of UNOS data determined the following to be predictors of allograft failure and need for retransplantation: location in the intensive care unit before transplantation, retransplantation, female donor to male recipient, age older than 44 years, and recipient race. While considering patients on the waiting list, remember to continue to reassess their medical conditions.

A decision is made to delist or temporarily deactivate patients from the transplant list if it is determined that the patient would not derive a survival benefit from the transplant, either from deterioration of their condition or rarely, from improvement to the point that the risks of LT now outweigh the benefits. Factors that have an adverse impact on the likelihood of posttransplant survival include mechanical ventilation, requirement for hemodialysis, fungal or resistant bacterial infections, and a previous transplant. When several of these factors are present, the posttransplant risk becomes prohibitive and transplant should be deferred.

Indications for Transplantation

LT is indicated in a variety of disease states ( Table 8-2 and Fig. 8-2 ). Specifically, when a patient develops sequelae of chronic liver disease such as portal hypertension or hepatocellular carcinoma, it is appropriate to refer for transplantation. Referral for transplantation should also be considered for the rare disease states in which the liver is not failing but causing other systemic disease (e.g., amyloidosis or oxaluria). The benefit of transplantation must be weighed against the considerable potential morbidity and mortality of undergoing a major surgical procedure. Therefore transplantation is generally reserved for those who are felt to have a poor quality of life and high mortality without transplant. Patients should be projected to have a longer life with transplant than in its absence, referred to as transplant survival benefit .