Why Liver Transplant Waitlists Might Misclassify High-Risk Patients

Why Liver Transplant Waitlists Might Misclassify High-Risk Patients

A new study has uncovered that the standard method for ranking patients on the waitlist for lifesaving liver transplantation may not prioritize some of the sickest candidates for the top of the list.

"Ultimately, we hope this information will help clinicians recognize that certain patients with a high risk of mortality may not be captured by our current organ-allocation policy," said Vinay Sundaram, MD, director of Hepatology Outcomes Research at the Cedars-Sinai Comprehensive Transplant Center. He is the co-first author of the multicenter study published recently in the peer-reviewed medical journal Gastroenterology, the most frequently cited journal in its field.

Liver transplants are performed as a last resort for liver failure, when the vital organ is too damaged to sustain life. The most common damage is caused by cirrhosis—severe scarring that can result from various conditions, including injuries, the hepatitis C virus, metabolic disease and long-term alcohol abuse. While more than 8,000 liver transplants were performed in the U.S. last year, the need exceeds availability of viable organs. According to the United Network for Organ Sharing (UNOS), the nonprofit that manages the U.S. organ transplant system, more than 13,000 patients were on its liver-transplant waitlist as of Jan. 18.

To decide which patients should be first in line for liver transplants, medical professionals rely on a standardized assessment of liver and kidney function known as the MELD (Model for End-Stage Liver Disease) score. The goal is to determine who among the many patients needing transplants are the sickest and yet also able to withstand surgery and to recover and thrive. A lower score indicates less urgency for a transplant; a higher score indicates greater urgency.

The study found that the MELD score does not fully identify patients with a life-threatening syndrome known as ACLF-3, or acute on chronic liver failure grade-3. This syndrome involves a sudden worsening of chronic liver failure accompanied by multiple organ-system failures, such as circulatory, respiratory or neurologic failures.

"ACLF-3 patients, even with relatively low MELD scores, have the highest risks of being removed from the waitlist due to being too sick for a transplant or of dying while waiting for a liver transplant," Sundaram said. "We sought to understand how this happens and how the standardized system of prioritization can unintentionally disadvantage these patients."

The team analyzed UNOS data from 100,594 patients on liver-transplant waitlists from 2005 through 2016.

"Our study goals were twofold," Sundaram said. "First, we set out to determine the mortality rate of patients with ACLF-3 awaiting liver transplantation, and second to analyze how patients with ACLF-3 fared when they did receive liver transplants."

Sundaram said the team discovered that ACLF-3 patients are sicker than the MELD scores would indicate because that assessment takes into account only liver and kidney function, whereas ACLF-3 patients have other organ-system failures as well. They found that nearly 44 percent of ACLF-3 patients in a certain category died or were removed from the transplant waitlists within 28 days of listing.

The team also found that when transplants were performed within 30 days of ACLF-3 patients being placed on the waitlists, their one-year post-transplant survival rate was more than 80 percent—equivalent to patients without this syndrome.

They concluded that ACLF-3 classification may help identify candidates on the list who are at high risk for short-term mortality. "Time is of the essence because it is clear that survival declines with increased waiting time for these patients," Sundaram said.

Rajiv Jalan, MD, PhD, of UCL Medical School, London, is co-first author of the study, along with Sundaram. Robert J. Wong, MD, from the Alameda Health System, Highland Hospital, in Oakland, Calif., is the senior author. The study also involved Loma Linda University in Loma Linda, Calif., and Baylor University Medical Center in Dallas.

"This study makes a major step toward improving the clinical relevance of waitlists for liver transplant candidates," said Andrew S. Klein, MD, the Esther and Mark Schumann Chair in Surgery and Transplantation Medicine, director of the Cedars-Sinai Comprehensive Transplant Center, professor of Surgery and a co-author of the study. "If further research expands and confirms these findings, they can lead to better transplant outcomes."

The Cedars-Sinai Comprehensive Transplant Center recently was reported by the Scientific Registry of Transplant Recipients to have the best one-year survival outcome for liver transplants of all hospitals in California.

DOI: 10.1053/j.gastro.2018.12.007

New Issue - Clinical Liver Disease: Liver Transplantation

Clinical Liver Disease: New Issue Now Available

August 2013
Volume 2, Issue 4
Pages 145–196

In the U.S., 7000 people per year receive a liver transplant, but thousands more wait for an organ to become available. This issue of Clinical Liver Disease (CLD), guest edited by Dr. Norah Terrault, explores the current topics and controversies in the field of liver transplantion, from refining the criteria used for selection, to managing infection before and after the operation.

Clinical Liver Disease (CLD) is the latest online learning resource of AASLD. Clinical in focus, CLD blends text, audio, video, webinars, and other interactive content into educational interventions launched every two months. These interventions are designed for any physician or healthcare provider caring for a patient with liver disease.

Selection for liver transplantation (pages 145–147)
Adam Peyton and Paul Martin
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.218
Abstract
Full Article (HTML)
PDF(380K)
 
MELD score, allocation, and distribution in the United States (pages 148–151)
Joel P. Wedd, Ann M. Harper and Scott W. Biggins
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.233  
Abstract
Full Article (HTML)
PDF(506K)
 
Donor and recipient effects on graft and patient survival (pages 152–155)
JP Norvell and Josh Levitsky
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.223
Abstract
Full Article (HTML)
PDF(429K)

Expanding the donor pool in liver transplantation: Extended criteria donors (pages 156–159)
Andrew S. deLemos and Parsia A. Vagefi
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.222
Abstract
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PDF(509K)

Current state of living donor liver transplantation (pages 160–164)
Paige M. Porret and Kim M. Olthoff
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.231
Abstract
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Acute liver failure: Peritransplant management and outcomes (pages 165–168)
Oren K. Fix
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.219
Abstract
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Hepatitis B virus: Prevention of recurrent infection (pages 169–172)
Federico G. Villamil and Fernando M. Cairo
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.224
Abstract
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Hepatitis C virus: Antiviral therapy in wait-listed patients (pages 173–176)
Asmeen Bhatt and Gregory T. Everson
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.225
Abstract
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Hepatitis C virus: Management of recurrent disease (pages 177–180)
Elizabeth C. Verna
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.220
Abstract
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PDF(440K)

Common problems in liver allograft biopsy interpretation: Resolving clinical dilemmas (pages 181–187)
Oyedele A. Adeyi
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.229
Abstract
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Immunosuppression: Conventions and controversies (pages 188–191)
Neil Mehta and Ryutaro Hirose
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.221
Abstract
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The liver transplant operation (pages 192–196)
Charles Miller and Teresa Diago Uso
Article first published online: 19 AUG 2013 | DOI: 10.1002/cld.232
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Baseline MELD Score Predicts Hepatic Decompensation during Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

Research Article

Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis 

Citation: Dultz G, Seelhof M, Herrmann E, Welker M-W, Friedrich-Rust M, et al. (2013)
Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis.
PLoS ONE 8(8): e71262. doi:10.1371/journal.pone.0071262

Editor: James Fung, The University of Hong Kong, Hong Kong

Received: February 28, 2013; Accepted: June 27, 2013; Published: August 1, 2013

Copyright: © 2013 Dultz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

Introduction Only

Full Text Available @ PLOS ONE....

Chronic hepatitis C virus (HCV) infection is a major health burden with more than 170 million infected individuals worldwide. Progression to liver cirrhosis is observed in 2–35% of the patients after 20–25 years of chronic infection and once liver cirrhosis is established, the cumulative 5-year risk to develop hepatocellular carcinoma (HCC) is estimated to be 17% [1], [2].

For more than one decade, available antiviral treatment consisted of a dual therapy with pegylated interferon alfa-2a or -2b (peginterferon) in combination with the guanosine analog ribavirin leading to sustained virologic response (SVR) rates in approximately half of the patients [3], [4]. Licensing of the new HCV protease inhibitors boceprevir and telaprevir, as part of a triple therapy for untreated HCV genotype 1 patients and those who failed previous treatment, represents a milestone in HCV treatment. Untreated patients undergoing triple therapy achieve significantly higher SVR rates (66–75%) as compared to those receiving the dual therapy alone (37–44%) [5], [6], [7]. Patients with a previous virologic relapse, partial response, or non-response to peginterferon and ribavirin also benefit when retreated with boceprevir or telaprevir-containing triple therapies [8], [9].

It is well established, that the presence of advanced fibrosis or compensated liver cirrhosis negatively influence a patient’s individual chance for achieving an SVR [10]. In turn, patients with advanced disease may benefit most from antiviral therapy since it was demonstrated in several long-term follow up cohort studies that SVR can prevent hepatic decompensation, development of hepatocellular carcinoma, and is associated with reduced overall mortality [11], [12], [13], [14]. Albeit still unsatisfactory, subanalyses of the pivotal boceprevir and telaprevir trials have shown that SVR rates for patients with advanced fibrosis and liver cirrhosis receiving triple therapy are higher as compared to those receiving peginterferon and ribavirin alone (52–62% vs. 33–38%) [5], [6].

In patients with more severe disease, e.g. patients with advanced cirrhosis and those on the waiting list for liver transplantation, successful antiviral therapy in selected cases may halt the progression of liver disease, can prevent HCV re-infection of the transplanted liver and subsequently leads to a decrease of post-transplant morbidity and mortality [15], [16], [17], [18], [19], [20]. However, SVR rates in those patients have been shown to be poorer (approximately 25%) and peginterferon and ribavirin in those patients is associated with potentially life-threatening side effects and discontinuation rates ranged from 20–100%.

Recently, preliminary data from the French early access program for telaprevir and boceprevir (CUPIC study) reporting antiviral efficacies and the occurrence of adverse events in more than 400 cirrhotic patients receiving antiviral triple therapy were presented [21]. About 38–48% of the cirrhotic patients experienced serious adverse events during the first 16 weeks of antiviral triple therapy and 8 patients died.

Thus, decision making for antiviral therapy in patients with (advanced) liver cirrhosis remains a clinical challenge facing the dilemma of increased SVR rates on the one hand and therapeutic schedules that are associated with increased complications and fatal outcomes on the other hand [22]. Moreover, predictive factors in cirrhotic patients that are associated with serious adverse events and/or hepatic decompensation during antiviral therapy are poorly defined.

The aim of this retrospective cohort study was to define baseline characteristics that can help to predict the risk for hepatic decompensation in HCV patients with advanced liver cirrhosis during antiviral therapy with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks.

Continue To Full Text Article

Watch Dr. Joe Galati - Calculating the MELD Score and How it Works

Liver Transplant Houston: Calculating the MELD Score and How it Works

by Dr. Joe Galati
on 03/22/2013

For those patients awaiting a liver transplant, the MELD score, which is a number calculated by evaluating the bilirubin, creatinine, and INR, is what the allocation of donor livers is based on. The higher the MELD score, the more likely you will get a liver transplant. At the same time, the higher the MELD score, the greater chance of life threatening complications. The majority of deaths that occur on the liver transplant waiting list take place in those patients with the highest MELD scores.

This video outlines some of the features of the MELD score calculation, and the potential for “MELD Exception” points to be added to the calculated MELD score.

I look forward to receiving your feedback.

Waiting for a Liver Transplant: My MELD Score is Low-Now What?

Waiting for a Liver Transplant: My MELD Score is Low-Now What?

by Dr. Joe Galati on 06/14/2012

Model for end-stage liver disease, also known as the MELD score, is the most commonly discussed topic when meeting with our liver transplant waiting list patients. Discussing the MELD score is the most anxiety provoking part of any conversation that we have with our patients. The reason it raises such anxiety is because the decision on who is allocated a donor organ is based on an individuals MELD score. Those with high scores receive a new liver, while those with lower scores continue to sit and wait on this guidelines. While no system is perfect on how to allocated donor livers, the MELD score works out for the majority of patients. What I’d like to discuss here is what happens to patients that have a low MELD score, and how they deal with the waiting time, as well as the emotions associated with it.

Without going into the complex calculations in determining how the MELD score is calculated, simply realize that sicker patients, for most part, have a higher score. As we have discussed in other entries, the MELD score is calculated the patient’s creatinine, bilirubin, INR. These are all laboratory tests that are routinely obtained in our patients with cirrhosis. It has been previously determined that the higher the MELD score, the lower the survival is. Based on this fact, it has been agreed that those patients with the lowest survival rates receive donor livers first. Generally speaking, the MELD score will range between values of 5 through 40. Based on prior research, a MELD score of 40 or greater is associated with a 71% 3 month mortality. In simple terms, this means that there is a 71% chance that an individual will not survive the next 3 months. Similarly, a MELD score between 30-39 as a mortality of 53%, and scores between 20 and 29 have a 20% three-month mortality. Of interest, MELD scores of 15 or less have improved survival and only a 2-6% chance of dying. Many liver transplant programs, based on these survival statistics, preferred not to place patients on the active liver waiting list until there MELD score is 15 or greater. There is some research that suggests transplanting patients with very low MELD score is is associated with a worse outcome, and survival. As we say many times with our patients, being a little sick with cirrhosis and liver disease may not be enough to get you a transplant, but being too sick, with MELD scores greater than 40, may put you in the position where you are too sick to survive with good outcomes.

There is no doubt that we take care of many patients that have a low MELD score, associated with a statistically ok survival, yet they are plagued by numerous incapacitating symptoms. Many of these patients are unable to work, participate in usual family activities, and are constantly visiting their are numerous physicians, having frequent hospital admissions. There is a subset of patients that fall into this category, creating a very frustrating situation for both the patient and their family, as well as for the the physicians, nurses, and surgeons. As I mentioned at the beginning of this entry, this is a great source of anxiety, and regular topic of conversation. Patient’s have a difficult time understanding how they can be so sick, yet they are low on the organ allocations list. Despite their disabilities and frequent hospitalizations, they are very far from receiving a liver transplant. So, what are they to do?
The discussion I have with patients regarding this is usually well received. Unfortunately, there are patients that are frustrated with the system and feel as if they are somehow being discriminated against because of their low MELD score. Time and time again, we explain to the patient and their family how the scoring system works, and the rationale behind. Nobody ever wants to here that there is someone worse off then them, but that this is the very nature the system.

Patients that have a low MELD score need to remain fully engaged with the their health care. They need to remain as physically active as possible, so that they’re able to maintain their strength and physical conditioning. Walking, light exercises with weights, swimming, and general physical activity around their house is key. The important point is that this is done on a regular basis, which ideally would be at least 5 days per week. Excessive sleeping, sitting, and general lack of activity will ultimately have a negative impact on both their current status, as well as how they bounced back after successful liver transplant surgery.

In addition to physical activity, maintaining a healthy diet is equally important. For most of our patients with cirrhosis, portal hypertension, and chronic liver disease, they need to maintain a low salt diet. We generally recommend a diet that contains less than 2000 mg of sodium per day. In some cases, we would like this to be 1500 mg of sodium per day. To maintain such a strict diet, you need to consume fresh fruits and vegetables, and fresh lean meat or fish. I tell all my patients that they need to avoid any foods that come from a box, can, or bag. Eating out, even in what appears to be a high-quality restaurant, we’ll only serve you food that is overly salted, high in fat, and high in calories. There is almost no way that you can maintain a low salt diet to this degree by eating out. Excessive salt in the diet will lead to fluid retention which is a major reason for both physician visits, as well as repeat hospitalizations.

In addition to physical activity and nutrition, patients with a low MELD score need to remain compliance with all of there medications. If you were having any side effects from the medicine, speak with your physician and liver transplant team. Likewise, discontinue medications on your own will lead to problems. Resuming the medications that previously were discontinued, can also lead to problems.

Patients that have a low MELD score need to remain optimistic and not lose hope. This system is not perfect, but generally works in most situations. The reality is that we do not have enough donated organs to share, and this is what leads to problems. Nationally, 30% of patients waiting for a liver transplant do not survive. Patient’s come to our liver transplant programs very late in their disease, when we have very little opportunity to change their course. Patient’s that are referred early, generally will have better outcomes, but at the same time, we will be caring for a lot of low MELD score patients. MELD scores are recalculated every time blood work is obtained, updating there status within the UNOS database. Based on the 3 parameters that are entered into the computer, complications such as infections or bleeding will results in the increase of the MELD score. While no one like to see these complications, which can be life-threatening, they do results higher MELD scores.

Source - The Blog of Dr. Joseph S. Galati
Discussions about the liver and everything else related to health and wellness

Gender disparity and MELD in liver transplantation

Volume 55, Issue 2, Pages 500-501 (August 2011)

Gender disparity and MELD in liver transplantation

Evangelos Cholongitas

Michael Thomas

Marco Senzolo

Andrew K. Burroughs

Received 1 January 2011; accepted 11 January 2011. published online 21 March 2011.

Refers to article:
Gender, renal function, and outcomes on the liver transplant waiting list: Assessment of revised MELD including estimated glomerular filtration rate , 03 November 2010
Robert P. Myers, Abdel Aziz M. Shaheen, Alexander I. Aspinall, Robert R. Quinn, Kelly W. Burak

Journal of Hepatology
March 2011 (Vol. 54, Issue 3, Pages 462-470)
Abstract | Full Text | Full-Text PDF (859 KB) | Add-Ons
,
Article Outline

• Conflict of interest

• References

• Copyright

We read with great interest the paper by Myers et al. [1], recently published in Journal of Hepatology, regarding the disparities between males and females in the MELD-based allocation system for liver transplantation. The authors found that women are disadvantaged under MELD, which may be attributable to the use of serum creatinine (Cr) in MELD score equation [1]. This confirms our previously published work indicating a systematic bias against women [2]. It is known that Cr is an inaccurate marker of renal function, since its concentration is influenced by several factors unrelated to renal function, such as total muscle mass, leading to discrepancies in Cr concentration between individuals with the same renal function [same glomerular filtration rate (GFR)] but of different age, race and sex [3].

We showed that Cr and GFR in females were lower than males, and female gender might negatively influence the chances of receiving a liver transplant with respect to men [2]. Correcting Cr by equalising the GFR between men and women, resulted in an increase in MELD score by up to 3 points in female LT candidates [2]. Following this, Moylan et al. evaluated the UNOS database [4] and showed that women were more likely to die on the waiting list in the post-MELD era, compared to the pre-MELD one, although women were listed with lower median MELD scores, compared to men (14 vs. 15, p<0.001) [4]. In the UNOS database, Myers et al. [1] found the same discrepancies, as we did [2]: women, compared with men, had lower Cr (0.9 vs. 1.0mg/dl, and MELD 16.5 vs. 17.2, both p<0.001), but worse renal function (estimated GFR: 72 vs. 83mL/min, p<0.001); however they were less likely to undergo liver transplantation (LT), and had greater 3-month mortality. Interestingly, Myers et al. [1] also found that patients with cirrhosis with a black ethnicity had a lower mortality, compared to white ethnicity. We believe that this likely to be related to Cr: black patients as a group have a higher Cr (more muscle mass), compared to white, for the same renal function, and, thus, MELD score may overestimate the severity of their liver disease. Indeed, MDRD calculations of GFR commonly have a correction factor for black race.

However Myers et al. did not find that using a calculated GFR (eGFR based on MDRD formula) helped to discriminate a different prognosis for men vs. women [1]. However, the evaluation with eGFR (MDRD formula), and not with “true” GFR using a gold standard method, could explain the discrepant results regarding the comparison presented of MELD-(Sodium)-eGFR and MELD-(Sodium) as the authors themselves suggested [1]. In contrast, Lim et al. [5] (using 125I-iothalamate for true GFR) found that “true” GFR was superior to Cr in assessing mortality risk on the waiting list and its incorporation in the MELD score (in the place of Cr), led to a significant improvement of discriminative ability of MELD. Unfortunately, Lim et al. [5] did not evaluate the prognostic impact of MELD-Cr and MELD-GFR scores in men and women candidates separately.

Secondly, it is possible that the higher mortality of women placed on waiting lists for liver transplantation [1], [4], compared to men, could be related to the presence of significant differences for matching of donor organ size to either recipient men or women, and thus, longer waiting times for women compared to men. Unfortunately, Myers et al. [1] did not evaluate this parameter. However, Lai et al. [6] recently suggested that height contributes to the gender disparity, possibly reflecting differences in transplantation rates for shorter individuals. The authors showed that short stature is related with higher risk of death for both men and women. Since women have shorter stature, compared to men, this could explain the higher waiting list mortality of women. However, data regarding the waiting time between men and women, or between different heights of candidates were not provided, and height cannot totally explain this disparity. Thus, as the authors recognized [6], further investigation is needed to clarify the issue of gender disparity and organ allocation in liver transplantation.

Nevertheless, it seems that female gender predicts lower transplantation rates, independently of height. A further recent study [7] again showed that women had lower transplantation rates and a substantially higher mortality risk on the LT waiting list, particularly when eGFR was between 15 and 30ml/min, due to underestimation of renal dysfunction in women, when Cr was used for MELD score calculation.

As we stated [2], we believe that a correction factor for gender and ethnicity should be introduced for equitable allocation in liver transplantation particularly if a MELD based system is used. As “true” GFR is difficult to perform routinely, and new serum markers, such as cystatin C and its mathematical formulae, seem to offer no significant advantage, compared to Cr and the MDRD formula, in patients with cirrhosis [8], a different parameter is needed. Thus, a simple increase of points should be instituted for women awaiting LT when MELD is used, or indeed in other formulae that use Cr, as unequal access to transplantation between men and women has now been shown by several groups [1], [4], [6], [7] following our first report [2].

References
[1]. [1]Myers RP, Shaheen AA, Aspinall AI, Quinn RR, Burak KW. Gender, renal function, and outcomes on the liver transplant waiting list: Assessment of revised MELD including estimated glomerular filtration rate. J Hepatol. 2011;54(3):462–470. Abstract | Full Text | Full-Text PDF (858 KB) | CrossRef

[2]. [2]Cholongitas E, Marelli L, Kerry A, Goodier DW, Nair D, Thomas M, et al. Female liver transplant recipients with the same GFR as male recipients have lower MELD scores – a systematic bias. Am J Transplant. 2007;7(3):685–692. MEDLINE | CrossRef

[3]. [3]Cholongitas E, Shusang V, Marelli L, Nair D, Thomas M, Patch D, et al. Review article: renal function assessment in cirrhosis – difficulties and alternative measurements. Aliment Pharmacol Ther. 2007;26(7):969–978. CrossRef

[4]. [4]Moylan CA, Brady CW, Johnson JL, Smith AD, Tuttle-Newhall JE, Muir AJ. Disparities in liver transplantation before and after introduction of the MELD score. JAMA. 2008;300(20):2371–2378. CrossRef

[5]. [5]Lim Y, Larson T, Benson J, Kamath P, Kremers W, Therneau T, et al. Serum sodium, renal function and survival of patients with end-stage liver disease. J Hepatol. 2010;52:523–528. Abstract | Full Text | Full-Text PDF (573 KB) | CrossRef

[6]. [6]Lai JC, Terrault NA, Vittinghoff E, Biggins SW. Height contributes to the gender difference in wait-list mortality under the MELD-based liver allocation system. Am J Transplant. 2010;10(12):2658–2664. CrossRef

[7]. [7]Mindikoglu AL, Regev A, Seliger SL, Magder LS. Gender disparity in liver transplant waiting-list mortality: the importance of kidney function. Liver transpl. 2010;16(10):1147–1157. CrossRef

[8]. [8]Xirouchakis E, Marelli L, Cholongitas E, Manousou P, Calvaruso V, Pleguezuelo M, et al. Comparison of Cystatin C and Creatinine-based Glomerular Filtration Rate Formulas with 51Cr-EDTA Clearance in Patients with Cirrhosis. Clin J Am Soc Nephrol. 2011;6(1):84–92. CrossRef

4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Greece

The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery UCL, Royal Free Hospital, London, UK

Department of Biochemistry, Royal Free Hospital, London, UK

The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery UCL, Royal Free Hospital, London, UK

The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery UCL, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK

Tel.: +44 20 74726229; fax: +44 20 74726226

PII: S0168-8278(11)00268-6

doi:10.1016/j.jhep.2011.01.054

© 2011 European Association for the Study of the Liver. All rights reserved.

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

June/July 2011 Gastro.org .
.
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 3.6.4.5).

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.

References
1. http://www.unos.org/ .

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.

Update;MELD score and Liver Transplant

The MELD Score and Liver Transplant: An Update for Patients

by Dr. Joe Galati on February 2, 2011


Liver Transplant

Patients awaiting transplant commonly have questions regarding there MELD score, and how this number is determined. As you can imagine, there is great anxiety in patients awaiting transplant. At almost every clinic visit, patients are asking for they’re updated score. In my own practice, at every visit we calculate the new score and discussed this result with them. The MELD score, which we have been using for the past several years, is calculated by taking the patient’s most recent bilirubin, creatinine, and INR, which is then entered into the computer and calculated. Theoretically, the MELD score can arrange in values between 5 and 40. It has generally been accepted that patients with a MELD score less than 15 have a better survival is not transplanted. Those with scores over 15 should be considered for transplant.

The higher the MELD score, the more ill the patient is, with a greater likelihood of not surviving. In the greater Houston area, most of the transplant programs, including ours at the Methodist Hospital, are transplanting patients with MELD score is greater than 25.

There are certain exceptions to the MELD score. Many of these are developed regionally. With patients who develop hepatocellular carcinoma, in most cases, they will receive a MELD exception of 22 points, even if they have a lower calculated score as described above. It’s been well established that patients with liver cancer should be transplanted quickly. This MELD exception allows this to take place.

If after 3 months the patient is not transplanted, additional points are granted. Other MELD exceptions for pulmonary hypertension, refractory gastrointestinal bleeding, and refractory ascites are also allowed. These are given on a case by case basis after a regional review by other transplant centers. Not every exception is granted, and this could be another source of anxiety for patients and their family.
Looking at the bilirubin, creatinine, and INR, you could see that as the patient becomes more ill, their MELD score will reflect a higher value.

It is very difficult to sit with the patient who has a low MELD score, who happens to feel very ill, and tells him that they must continue to get even more debilitated before a transplant is performed. While the current allocations system works for the vast majority of patients, there are always going to be those patients that have a MELD score that does not accurately represent how sick they are. For these patients, this is where most of the anxiety and concern is present. The best that we can do as physicians and other healthcare providers is to reassure them and worked very closely with them. I personally have been involved in liver transplantation for over 20 years, and the same issues we faced 20 years ago, despite a different allocations system, remained today.

To calculate your own MELD score, I have listed a link below. Of course, if you have any questions, feel free to contact me or post your comments on this blog for others to see and learn from. You can always reach me at Liver Specialists of Texas at 713-794-07 00.
Calculate your MELD score here.

MELD score is fair to patients waiting for liver re-transplant:study

MELD score is fair to patients waiting for liver re-transplant: study
Last Updated: 2010-12-27 9:00:14 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The current U.S. system for allocating donated livers - which is based on the Model for End-Stage Liver Disease (MELD) score - is fair to patients with chronic liver disease whether they're waiting for a first transplant or a retransplant, a new study shows.

The MELD score, adopted in 2002, considers the patient's bilirubin level, creatinine level, and international normalized ratio. Increasing scores indicate a higher short-term risk for death without a transplant.

Patients with fulminant liver failure, or those who've just had a transplant but have primary graft nonfunction or early hepatic artery thrombosis, always move to the top of the waiting list, with a "status 1" priority.

But patients with chronic liver disease compete under the same system whether they're waiting for a retransplant or a primary transplant. Patients and doctors have wondered whether chances of a new liver - and odds of survival -- differ depending on whether a candidate has already been transplanted before. In a study reported online November 10th in the American Journal of Transplantation, Dr. H. J. Kim and colleagues from the Mayo Clinic in Rochester, Minnesota compared the two groups' mortality rates within six months of being listed for transplant with a given MELD score. They also compared current findings to results in a pre-MELD era.

"The main finding in our analysis is that in the MELD score ranges where most liver transplantation is performed, there were no large differences in waitlist mortality given a MELD score," the researchers report. "In our opinion, the difference was not large enough to warrant an adjustment in the allocation system."

They had data on roughly 30,000 patients who joined the waiting list in the MELD era (including nearly 1400 needing retransplant), and roughly 15,000 registered in the two years before MELD was adopted (with almost 700 needing retransplant).

In the MELD era, retransplant candidates had higher median scores at the time of registration than primary transplant candidates (21 versus 15, respectively), and this likely contributed to the higher 6-month waiting list mortality among retransplant candidates on an unadjusted Kaplan-Meier analysis.

As expected, MELD score at registration was associated with increasing risk of death on multivariate analysis -- but the slope of the survival curve was slightly steeper for primary transplant candidates than for retransplant candidates. As a result, the risk of death in retransplant candidates was higher than that for primary transplant candidates in the low MELD score range and lower than that for primary transplant candidates in the high MELD score range.

The probability of actually receiving a liver transplant within 6 months of registration increased substantially from the pre-MELD era (28% for retransplant candidates, 19% for primary transplant candidates) to the post-MELD era (54% for retransplant candidates, 35% for primary transplant candidates).

Six-month waitlist mortality also decreased significantly between the periods (from 18% to 14% for retransplant candidates and from 9.3% to 8.0% for primary transplant candidates).

"This analysis contributes to the dialogue by providing a quantitative basis upon which philosophical and ethical considerations may be made," the investigators conclude. "In the meantime, we are mostly comforted by the fact that MELD, shown here again as a strong indicator of waitlist mortality, has contributed to a significant increase in the probability of receiving transplantation under the current allocation system."

SOURCE: http://link.reuters.com/kuq52r

Am J Transpl 2010.