MELD may not be the better system for organ allocation in liver transplantation patients in Singapore.

Abstract

The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore.
There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method.
The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35).
MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Full text

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Singapore Med J 2006; 47(7) : 1
Singapore Med J 2006; 47(7) : 592
ABSTRACT
Introduction: The Model for End-Stage Liver
Disease (MELD) score is a good predictor of
mortality on the liver transplant waiting list
and is the current system of organ allocation
in the USA. However, a higher MELD may be
associated with poorer outcome post-liver
transplantation. The aim of this study was to
determine if MELD should be implemented
as the system for organ allocation for liver
transplantation in Singapore.
Methods: There were 46 adult patients who
underwent primary liver transplantation at
the National University Hospital, Singapore
from January 1996 to December 2002. We
applied the MELD score to patients who were
transplanted and looked for a correlation
with survival post-transplant. Patients were
followed-up until the most recent visit or
death. Survival analysis was performed using
Cox regression and Kaplan-Meier method.
Results: The mean age at transplant was 52.7
(SD 2.34) years. The majority of the patients
transplanted had Hepatitis B (43 percent).
The median MELD score at transplantation
was 17 (7-42) and the median Child’s score was
11 (6-15). There was a significant correlation
between pre-transplant MELD and survival
at six months (p-value is 0.037, 95 percent
confidence interval [CI] is 1.004-1.13) but
not at one year (p-value is 0.065, 95 percent
CI is 0.99-1.12). There were no differences in
the pre-transplant MELD (odds-ratio [OR]
1, 95 percent CI 0.9-1) as well as survival for
patients with and without Hepatitis B (OR
0.72, 95 percent CI 0.22-2.35).
Conclusion: MELD allows livers to be allocated
to the patients with the greatest medical
urgency but its influence on post-transplant
survival should be further clarified so that
post-transplant survival is not compromised.
MELD may not be the better
system for organ allocation in liver
transplantation patients in Singapore
Lee Y M, Fernandez M, Da Costa M, Lee K H, Sutedja D S, Tai B C, Tan K C, Isaac J,
Prabhakaran K, Lim S G
Department of
Gastroenterology
and Hepatology
National University
Hospital
5 Lower Kent Ridge
Road
Singapore 119074
Lee Y M, MBBS, MRCP
Consultant and Assistant
Professor
Fernandez M, MBBS,
MRCP
Registrar
Sutedja D S, MBBS,
FRCP, FAMS
Consultant
Lim S G, MD, FRACP,
FRCP
Senior Consultant and
Associate Professor
Liver Transplant
Programme
Da Costa M, RN
Transplant Coordinator
Department of Medicine
Lee K H, MBBS, FRCP
Senior Consultant and
Associate Professor
Centre for Molecular
Epidemiology
Tai B C, MSc, C Stat
Research Fellow
Asian Centre for
Liver Diseases &
Transplantation
Gleneagles Medical
Centre
6 A Napier Road
Singapore 258500
Tan K C, MBBS, FRCS
Consultant
Department of Surgery
Isaac J, MBBS, FRCS
Senior Consultant and
Associate Professor
Prabhakaran K, MBBS,
FRCS
Senior Consultant and
Associate Professor

Correspondence to:
Dr Seng-Gee Lim
Tel: (65) 6772 4369
Fax: (65) 6779 4112
Email: mdclimsg@
nus.edu.sg
O r i g i n a l A r t i c l e
Keywords: hepatitis B, liver transplantation,
MELD score, organ allocation
Singapore Med J 2006; 47(7):592-594
INTRODUCTION
In 2002, the Organ Procurement and Transplant
Network in the United States of America
implemented a new system, the Model for End-
Stage Liver Disease (MELD), for the allocation
of livers for transplantation according to disease
severity(1). The reason for this change was a result
of two studies which showed that waiting time
does not predict mortality on the waiting list for
liver transplant(2,3). MELD was to be superior to the
Child-Turcotte-Pugh (CTP) score in predicting three
months mortality among patients with chronic liver
disease on the liver transplant waiting list(4).
Currently, the system of organ allocation in
Singapore is based upon the CTP scoring system
and waiting time. MELD may be a more suitable
replacement as it allows livers to be allocated based
on medical urgency, and it is a more discriminatory
and objective scoring system than the CTP. At the
same time, there must be a balance between fairness
in organ allocation without compromising post-
transplant survival. The aim of our study was to
determine the median MELD at which patients are
currently being transplanted. We also wanted to
determine if there was a correlation between post-
transplant survival and pre-transplant MELD and
CTP scores. As hepatitis B is the main indication for
transplant in Singapore, we wanted to see if there
was any difference in MELD scores between patients
transplanted for Hepatitis B compared to those with
other aetiologies.
METHODS
We retrospectively studied the records of all adult
patients who underwent liver transplantation from
January 1996 to December 2002 at the National
University Hospital, which is the designated and sole
liver transplant centre in Singapore. There were no

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were also excluded. The final study group comprised
46 patients. The MELD immediately pre-transplant
were calculated from laboratory results within 24
hours of transplant according to the UNOS formula:
MELD = [0.957 × log e (Creatinine) + 0.378 × log e
(Bilirubin) + 1.12 × log e (INR) + 0.643] × 10.
Patients were followed-up until death occurred
or until the present time for those who are still
alive. We assessed if survival correlated with the
pre-transplant MELD scores. We then compared
the survival and pre-transplant MELD scores of
patients with and without Hepatitis B. Statistical
analysis was performed using Cox regression for
continuous variables and the Kaplan-Meier method
for categorical variables.
RESULTS
The demographical and clinical characteristics of the
46 study patients are shown in Table I. There were
altogether 46 adult patients included in this study.
The commonest indication for liver transplantation
was hepatitis B chronic liver disease with or without
hepatocellular carcinoma (HCC). At the time of
analysis, 11 deaths were reported. The causes of
death include sepsis (36%), primary non-function
(36%), ischaemic heart disease with cardiac failure
(18%), and hepatic artery thrombosis (9%).
The median MELD score at transplantation was
17 (7-42) and the median Childʼs score was 11 (6-15).
When the survival of patients with and without HCC
was compared, we found no difference in survival
between the two groups (hazardous ratio [HR]
0.72, 95% CI 0.21-2.49) (Fig. 1). We also found
that there was no significant influence of donor age
(HR 0.72, 95% CI 0.21-2.49), sex mismatch (HR 0.78,
95% CI 0.23-2.62) and cold ischaemia time (HR 1, 95%
CI 0.99-1) on post-transplant survival in our study.
The association between post-transplant survival
and pre-transplant MELD score was significant
at six months (p=0.037, 95% CI 1.004-1.13).
The association with post-transplant survival at one
year was not significant although there was a trend
towards increased mortality with higher pre-transplant
MELD scores (p=0.065, 95% CI 0.99-1.12). We
found no association between the pre-transplant
Childʼs score and post-transplant survival at six
months (p=0.27, 95% CI 0.88-1.59) or at one year
(p=0.136, 95% CI 0.93-1.6).
DISCUSSION
In Singapore, the prevalence of hepatitis B is 4%
and is the major indication for liver transplantation.
re-transplantations. One patient with fulminant
hepatic failure and another with pulmonary metastases
due to primary hepatocellular carcinoma were
excluded from the analysis. Three patients with data
unavailable for calculation of pre-transplant MELD
Fig. 1 Post-transplant survival of HCC versus non-HCC
patients.
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
Survival time (month)
Cumulative survival
5 10 152025 30
HR = 0.72 (95% Cl 0.21 to 2.49)
p = 0.620
HCC
Non-HCC
Table I. Clinical and demographical characteristics
of patients.
n=46
Age in years
Mean (SD) 52.7 (2.34)
Gender (%)
Male
Female
37 (80%)
9 (20%)
Race (%)
Chinese
Indian
Malay
Others
33 (72%)
8 (17%)
1 (2%)
4 (9%)
Type of liver transplant (%)
Cadaveric
Living-related, right lobe
Living-related, left lobe
42 (91%)
2 (4%)
2 (4%)
Hepatitis B (%)
Yes
No
20 (43%)
26 (57%)
Hepatocellular carcinoma (%)
Yes
No
15 (33)
31 (67)
MELD score
Median (range) 17 (7-42)
Child’s score
Median (range) 11 (6-15)

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Orthotopic liver transplantation (OLT) has become
a viable option since the advent of nucleoside
analogues giving excellent outcomes for Hepatitis B
patients undergoing OLT. Although the number on the
waiting list has grown considerably, this has not been
matched by the number of organ donors. Therefore,
it is necessary to review our current system of organ
allocation such that it is fair and objective, and also
allows the best utilisation of resources.
From our single centre study, the median MELD
score at transplant was 17, which is similar to
the median score of 18 or lower in 92% of liver
transplants done in the USA(5). This appears to be
an optimum time for transplantation as the post-
transplant survival is good. This gives the physicians
an indication when a patient should be worked up
for transplant for optimal utilisation of resources.
We have also shown that there was no difference
in pre-transplant MELD scores and post-transplant
survival between patients with hepatitis B and those
with other disease aetiologies. This is important
as hepatitis B is the main indication for liver
transplantation in Singapore and most of Southeast
Asia. As MELD is a continuous score, there will
be no ambiguity or subjectivity in the allocation
of livers. Therefore, there is a strong case for the
implementation of MELD in Singapore.
However, our study also shows that post-
transplant mortality at six months correlates
significantly with pre-transplant MELD. This implies
that by transplanting the sickest patients first, we
may also be increasing the morbidity and mortality
post-liver transplant. A recent study from the USA
has shown that post-transplant survival up to two
years was significantly lower in groups with higher
MELD score(6). In our study, there was only a trend
towards higher mortality at one year with higher
MELD scores. This may be because pre-transplant
disease severity has the most impact in the early
period post-transplant while mortality in the later
period is influenced by other factors such as disease
recurrence and chronic rejection. In addition, Saab
et al(7) found that a significant increase rate of death
in recipients of OLT with MELD scores higher than
36. However, whether a pre-transplant MELD of 36
should be the cut-off point for liver transplantation,
this must be validated in a prospective study. We
did not find any significant correlation between
the pre-transplant Childʼs score and post-transplant
mortality at six months and one year.
In conclusion, the MELD is more discriminatory,
objective and a better predictor of mortality on the
liver transplant waiting list than the Childʼs score.
It is indeed a fairer and more transparent system of
organ allocation. However, in view of its influence
on post-transplant survival, it is necessary to
ascertain if there is a MELD score beyond which
liver transplantation would be futile.
ACKNOWLEDGEMENT
We would like to thank Christina Yip of National
University Hospital for her help.
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