Thursday, July 14, 2011

What’s Up with the MELD Score? Its Future, Exceptions and Additions

June/July 2011 .
What’s Up with the MELD Score? Its Future, Exceptions and Additions

Nikolaos T. Pyrsopoulos, MD, PhD, MBA

Chief, Hepatology; Medical Director, Liver Transplant, Florida Hospital, Orlando; Associate Professor of Medicine, University of Central Florida, Orlando

Getting on a liver transplant list might be one of the most exciting moments of a patient’s life, as the potential of a second chance in life can be a reality. More than 120,000 patients are waiting for an organ graft and close to 17,000 for a liver (data accessed April 2011).1 But, not all of them will receive the call telling them, “There is an offer for you and you should come to the hospital as soon as possible,” as not all of the candidates will be transplanted. What determines the allocation of a graft is the patient’s blood type and the severity of the illness, among other things. Unfortunately, a liver graft can be considered a scarce commodity, as the demand is much higher than the supply. As transplant physicians, we always have in mind “ … and justice for all” when we deal with the liver transplant list, as “the sickest come first” and the allocation of the organ should be based on this concept. We also have to make sure that our patients are still eligible for a transplant while on the list, and update their status according to the guidelines.

In February 2002, the United Network for Organ Sharing (UNOS) mandated that the ranking of patients while on the list will be based on a more objective measurement model: the Model for End-Stage Liver Disease (MELD), transitioned from the Child-Turcotte-Pugh score.2 MELD was reported to be mortality predictive scoring for patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), taking into account three variables: bilirubin, international normalized ratio (INR) and creatinine.3 The implementation of the new model resulted in an approximately 15 percent decrease in deaths of the patients waiting for a graft, and the median waiting time from 656 to 416 days.4 The MELD scoring system is not without limitations. What about patients receiving Coumadin or having the INR checked in different laboratories (intra-laboratory variability)? What about patients with Gilbert syndrome (increased bilirubin)? What does a creatinine value represent?5 Is it the same for a man as for a woman, and an Asian patient in comparison to an African American patient?

Newer markers that are more accurate in predicting renal insufficiency in patients with cirrhosis and correlate with MELD should be identified. Is the range of the values included in the formula the most adequate? Can we optimize the coefficient of the formula? How about hyponatremia?

Table 1. Diseases in Which MELD Exception Can Be Granted
Liver transplant candidates with hepatocellular carcinoma (meeting certain criteria)
Liver candidates with hepatopulmonary syndrome (meeting certain criteria)
Liver candidates with cholangiocarcinoma (meeting certain criteria)
Liver candidates with cystic fibrosis (signs of reduced pulmonary function, defined as having an FEV1 that falls below 40 percent)
Liver candidates with familial amyloid polyneuropathy (meeting certain criteria)
Liver candidates with primary hyperoxaluria (meeting certain criteria)
Liver candidates with portopulmonary syndrome (meeting certain criteria)

A modification of the MELD has been reported; the Scientific Registry of Transplant Recipients proposed updated coefficients and eliminated upper or low bounds for the variable, including the assignment of creatinine of 4 mg/dl for patients receiving renal replacement therapy, which improved the 90-day predictability compared to the existing MELD.6 The MELD-Na incorporates the sodium level in the MELD formula, and it was reported that this addition will influence 27 percent of the patients listed, thus offering an improved predictability of risk of death within six months.7 The refit MELD includes sodium, changes of the values of the coefficients and changes of the bounds of the variables, though the upper bound of serum creatinine is 4 mg/dl, improving the waitlist mortality prediction.8

Portal hypertension is a very important issue that MELD underestimates. The etiology of liver disease is not taken into account as well. A list of diseases and disease severities was established to address instances that MELD cannot predict (table 1). However, occasionally, the list does not include conditions that might meet eligibility requirements for transplantation such as severe debilitating hepatic encephalopathy. In this case, a UNOS regional review board made up of transplant physicians and surgeons review a transplant center’s request for MELD exception for candidates with a low MELD. This is done on a case-by-case basis to identify patients that should be listed with a higher score than the one MELD predicts (UNOS policy

Unequivocally, I cannot see the MELD as just a scoring system published more than 10 years ago, predicting mortality for patients undergoing TIPS. Its current implementation is mainly as a powerful model determining — at a national and international level — who should be transplanted first while on the list. The refit MELD, incorporating changes such as the addition of sodium included in the formula and potential changes of the values of the variables already included in the formula, might be a solution so that the model will be more accurate and “ … justice for all” will be given at the highest degree.

1. .

2. Freeman RB Jr, Wiesner RH, Harper A, McDiarmid SV, Lake J, Edwards E, Merion R, et al. The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transpl 2002;8:851-85.

3. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. Apr 2000;31(4):864-871.

4. Wiesner RH, Edwards E, Freeman R, Harper A, Kim WR, Kamath PS, et al. Model for End-Stage Liver Disease (MELD) and Allocation of Donor Livers. Gastroenterology 2003;124:91-96.

5. Sharma P, Schaubel DE, Sima CS, Merion RM, Lok AS. Re-weighting the model for end-stage liver disease score components. Gastroenterology. Nov 2008;135(5):1575-1581.

6. W. Ray Kim WR, Scott W. Biggins SC, M.D., Walter K. Kremers WK, Wiesner RH, Kamath PS, Benson JT, Edwards E, Therneau TM. Hyponatremia and Mortality among Patients on the Liver-Transplant Waiting List. N Engl J Med 2008; 359:1018-1026.

7. Biggins SW, Kim WR, Terrault NA, et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. May 2006;130(6):1652-1660.

8. Leise MD, W. Ray Kim, Kremers WK, Larson JJ, Benson JT, Therneau TM. A Revised Model for End-Stage Liver Disease Optimizes Prediction of Mortality Among Patients Awaiting Liver Transplantation. Gastroenterology (Article in press PII: S0016-5085(11)00171-5 DOI: 10.1053/j.gastro.2011.02.017).

Author disclosure: Dr. Pyrsopoulos is on the advisory board for Bayer, Genentech, Gilead, Merck and Salix. He has given lectures under the direct sponsorship of Genentech, Merck, Onyx, Salix and Vertex. He received significant research support from Bayer, Bristol-Myers Squibb, Genentech, Gilead and Sanofi-Aventis. Dr. Pyrsopoulos is also a member of AASLD's Program Evaluation Committee and the United Network for Organ Sharing Region Three Board Review Committee.

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