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
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Article Outline
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.
<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.
ml/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.
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