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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”



    
LIVER TRANSPLANTATION
January 2003 . Volume 9 . Number 1
Editorial
 
Is the change in MELD score a better indicator of mortality than baseline
MELD score?
 
Patrick S. Kamath   W. Ray Kim
 
Liver transplantation should ideally be offered to the patient who has a
high risk of dying without liver transplantation, but who is likely to have
prolonged survival and improved quality of life posttransplantation.
Allocation systems for liver transplantation currently do not identify
patients who benefit the most from liver transplantation. Rather, the
systems are geared toward determining which patients should receive a donor
organ on a priority. Under the previous allocation system, for the vast
majority of patients, waiting time was the major determinant of liver
allocation.1 Patients disadvantaged by that system included sicker patients
with short waiting time, such as those patients with limited access to
medical resources who first receive medical attention when the liver disease
is advanced. In 1998, the Institute of Medicine suggested guidelines
de-emphasizing waiting time and mandated that the sickest patients be
highest on the priority list.2 Therefore, the emphasis changed from waiting
time to selecting the sickest patients for liver transplantation. It was
also obvious that the Child-Turcotte-Pugh classification, which categorized
patients with cirrhosis into only three groups (United Network for Organ
Sharing [UNOS] status 3, 2A, and 2B1) was not an optimal system for ranking
patients at risk for dying without liver transplantation.
    
 
The Model for End-stage Liver Disease (MELD) was developed initially to
determine risk of mortality in patients undergoing transjugular intrahepatic
portosystemic shunts (TIPS).3 This model was subsequently applied to
patients with end-stage liver disease not undergoing liver transplantation.
The model was further validated in outpatients with compensated cirrhosis
from Palermo, Italy; a cohort of patients entered into trials for treatment
of primary biliary cirrhosis; and, finally, in a historical cohort of
patients at a time when liver transplantation was not widely available.4 In
February 2002, the UNOS adopted MELD as the gauge by which to prioritize
organs for liver transplantation. However, the model had not been validated
specifically in a group of patients awaiting liver transplantation. Further,
it was not certain whether the variables used in MELD, namely the
coefficients for prothrombin time, expressed as the International Normalized
Ratio (INR), creatinine, and bilirubin were also applicable to patients
awaiting liver transplantation. Moreover, it was not known whether a certain
MELD score could be used as a cutoff to avoid futile transplantation.
 
In the current study, Merion et al5 have studied the utility of MELD in
determining survival in patients awaiting liver transplantation. They
studied MELD at the time of listing, updated MELD scores, as well as the
change in MELD over 30 days. They compared MELD against the
Child-Turcotte-Pugh score on which the previous allocation system, namely
UNOS status 2A, 2B, and 3, was based. They concluded that MELD was superior
to the Child-Turcotte-Pugh classification, as well as the UNOS status.
Moreover, they showed that a change in MELD over 30 days was a more
significant determinant of mortality than a one-time MELD score. For
example, they showed that for a patient with a MELD score of 25 who has a
stable score for a month ( MELD = 0), the mortality was lower than in a
patient in whom the MELD score had increased over a month to 25 (positive
MELD), but higher than in patients with a decreasing MELD score over the
previous 30 days (negative  MELD). What do these findings mean and how
should they be applied in the allocation of organs for liver
transplantation?
 
The MELD score will change with variations in the prothrombin time, serum
bilirubin, and serum creatinine. An increase in score generally indicates
more severe liver disease, and the MELD score may not decrease if the change
is truly related to worsening in liver function, that is, further
decompensation of the liver disease. On the other hand, MELD changes may be
transient and reversible if related to factors such as dehydration,
infection, etc. Thus, the serum creatinine level may increase with
over-enthusiastic use of diuretics, or if the patient has correctable
intrinsic disease; bilirubin and creatinine levels may increase with sepsis;
and prothrombin time may be prolonged in a patient in an intensive care unit
who is not on oral nutrition and is on systemic antibiotics, which causes
vitamin K deficiency. MELD scores, therefore, may increase because of
factors not directly related to worsening of liver disease. On the other
hand, a decrease in MELD score probably indicates correction of a reversible
factor and incorrect application of the MELD scoring system. Accordingly,
before the conclusions of this study are accepted, it is essential to know
what the cause of improving MELD or worsening MELD score in these patients
was. One would suspect that some of the patients who had a rapid increase in
MELD score over 30 days had spontaneous bacterial peritonitis resulting in
hepatorenal syndrome, or sepsis resulting in an increase in serum values for
creatinine, bilirubin, and prothrombin time, and thus an increase in the
MELD score. Similarly, those who had a decrease in MELD score probably had
reversible factors that were corrected. Merion et al suggest that  MELD be
used as a tiebreaker for organ allocation in patients on a waiting list for
liver transplantation with identical MELD scores.5 Taking the example of
three patients with a MELD score of 25, the patient at highest risk of dying
would be the patient with a positive  MELD and so should receive a liver
transplant on higher priority than the other two patients. The patient with
a stable MELD score would have the next higher risk for mortality, and the
patient with a negative  MELD would have the least risk of mortality. Should
we in fact use the  MELD as a tiebreaker when patients have identical MELD
scores, allocating the organ to the patient with positive  MELD as opposed
to stable or negative  MELD?
    
 
When the MELD system was originally developed, scores were taken in patients
hemodynamically stable and great pains were taken to ascertain that all
reversible factors were corrected. Thus, serum creatinine levels were
recorded after the patients were deemed clinically to be isovolemic.
Patients with intrinsic renal disease, as well as hepatocellular carcinoma,
were excluded. In patients with sepsis, scores were recorded after the
infection had cleared and prothrombin time, serum creatinine level, and
serum bilirubin level were stable for a week. Therefore, MELD scores may not
be as accurate an indicator of mortality in patients with cirrhosis who have
intrinsic renal disease, are dehydrated, who are septic, or who have
hepatocellular carcinoma. The implication is that it would be unusual for
MELD to improve significantly once there are no reversible factors.
Moreover, in Merion's study, the increase in MELD may be a result of
multiorgan failure. In other words, an increase in MELD may in fact be part
of the event (that is, an agonal change) rather than a predictor of death.
However, if one can be certain that reversible factors have been ruled out,
and the increase in MELD is not a preterminal event, then the  MELD could be
used to break ties for patients with identical MELD scores. If, on the other
hand, the positive  MELD is related to sepsis, such patients may have a poor
outcome after liver transplantation.
 
One of our concerns had been that MELD as developed in patients undergoing
TIPS may not be the perfect model to determine either mortality in patients
awaiting liver transplantation or outcome posttransplantation. The current
study, however, confirms that INR for prothrombin time, serum creatinine
level, and serum bilirubin level are the most important determinants of
survival on a waiting list. Although further fine-tuning of the allocation
system using the MELD scale is necessary, continued vigilance is also
required to make certain that patients' correct MELD scores are being
entered. This would require that each center satisfy themselves that they
have corrected reversible factors before recording MELD scores. The current
study suggests that a more rapidly increasing MELD score is likely to be
associated with increasing mortality. If findings are confirmed in
prospectively collected data sets, patients with positive  MELD should
receive organs on priority as compared with patients with identical scores
but with unchanging MELD or negative  MELD.
 
The MELD scale is being used to determine which patients are most at risk
for mortality and thus are at priority for receiving organs for liver
transplantation. Ideally, the system should take into account
posttransplantation outcome so that patients benefit the most from liver
transplantation and futile transplantation is avoided. In addition, data
from Merion et al suggest that there is a need to determine whether patients
with rapidly increasing MELD score have a worse outcome after liver
transplantation. More importantly, the current study suggests that the
change in the allocation system from Child-Turcotte-Pugh score to MELD score
is a step in the right direction. Using a change in MELD score rather than a
single MELD score may be one further step in finding a system whereby the
benefits of liver transplantation are maximized.
 
 
   References
1.  Lucey MR, Brown KA, Everson GT, Fung JJ, Gish R, Keeffe EB, et al.
Minimal criteria for placement of adults on the liver transplant waiting
list: A report of a national conference organized by the American Society of
Transplant Physicians and the American Association for the Study of Liver
Diseases. Liver Transpl Surg 1997;3:628-637.MEDLINE
2.  Institute of Medicine. Analysis of waiting times. In: Committee on Organ
Procurement and Transplantation Policy, (ed). Organ Procurement and
Transplantation: Assessing Current Policies and the Potential Impact of the
DHHS Final Rule. National Academy Press, Washington, DC, 1999:57-78.
3.  Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, terBorg PL. A model
to predict poor survival in patients undergoing trans-jugular intrahepatic
portosystemic shunts. Hepatology 2000;31:864-871.MEDLINE
 4.  Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL,
et al. A model to predict survival in patients with end-stage liver disease.
Hepatology 2000;33:464-470.
5.  Merion RM, Wolfe RA, Dykstra DM, Leichtman AB, Gillespie B, Held PJ.
Longitudinal assessment of mortality risk among candidates for liver
transplantation. Liver Transpl 2003;9:12-18.
 
   Publishing and Reprint Information  From the Advanced Liver Diseases
Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic and
Foundation, Rochester, MN.
Address reprint requests to Patrick S. Kamath, MD, Division of
Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First St
SW, Rochester, MN 55905. Telephone: 507-284-1649; FAX: 507-284-0538; E-mail:
kamath.patrick@mayo.edu Copyright © 2003 by the American Association for the
Study of Liver Diseases 1527-6465/03/0901-0003$35.00/0
doi:10.1053/jlts.2003.50031

 

 

 

 

 

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