Early post-transplant survival: Interaction of MELD score and hospitalization status

doi:10.1016/j.jhep.2015.03.034

Journal of Hepatology

Volume 63, Issue 3, September 2015, Pages 601-608

https://doi.org/10.1016/j.jhep.2015.03.034 Get rights and content

Background & Aims

Urgency-based allocation that relies on the MELD score prioritizes patients at the highest risk of waitlist mortality. However, identifying patients at greatest risk for short-term post-transplant mortality is needed in order to optimize the potential gains in overall survival obtained through improved long-term management of transplant recipients. There are limited data on the predictive ability of MELD score for early post-transplant mortality, and no data assessing the interaction between MELD score and hospitalization status.

Methods

We analyzed UNOS data from 2002 to 2013 on 50,838 non-status 1 single-organ liver transplant recipients and fit multivariable logistic models to evaluate the association and interaction between MELD score and pre-transplant hospitalization status on short-term post-transplant mortality.

Results

There was a significant interaction (p <0.01) between laboratory MELD score and hospitalization status on three-, six-, and 12-month post-transplant mortality in multivariable logistic models. This interaction was most pronounced in patients with a laboratory MELD score <25 transplanted from an ICU, whose adjusted predicted three-, six-, and 12-month post-transplant mortality approximated those of patients with a MELD score ⩾30. Compared to hospitalized patients with a MELD score of 30–34, those with a MELD score ⩾35 in an ICU had significantly increased risk of three-month (OR: 1.54, 95% CI: 1.21–1.97), 6-month (OR: 1.35, 95% CI: 1.09–1.67), and 12-month (OR: 1.25, 95% CI: 1.03–1.52) post-transplant mortality.

Discussion

Pre-transplant ICU status modifies the risk of early post-transplant mortality, independent of MELD score. This should be considered when determining candidacy for transplantation in order to optimize efficient use of a scarce resource.

Graphical abstract

Introduction

Liver transplantation allocation in the United States (US) and in Europe operates under an urgency-based system, such that candidates with the greatest estimated waitlist mortality receive the highest priority. The determination of urgency is based solely on the Model for End-Stage Liver Disease (MELD) score, which is a reliable predictor of waitlist mortality in most patients [1]. Other measures of severity of illness, such as the need for hospitalization, either on a general medical ward or an intensive care unit (ICU) may modify the risk of waitlist mortality differentially based on a patient’s MELD score. Despite the emphasis placed on prioritizing the sickest patients for liver transplantation, such considerations may negatively impact the efficiency of a system that focuses on allocating a scarce resource, transplantable livers. With allocation policies in the US focused on giving even greater priority to patients with the highest MELD scores, such as the Share 35 policy initiated on June 18, 2013 that mandates broader regional sharing of organs to patients with a MELD score ⩾35, there is the potential for downstream consequences with regards to maximizing use of a limited supply of organs. Concerns have been raised about the impact of this policy on post-transplant morbidity and mortality because of increased transplantation of “sicker” patients, defined as those with higher MELD scores. Severity of illness, and its impact on post-transplant mortality, may in fact be related to a combination of MELD score and other factors, notably hospitalization status prior to transplantation.

Several studies have evaluated the ability of the MELD score to predict post-transplant mortality with mixed results [2], [3], [4], [5]. In Europe, a number of previous studies demonstrated an increase in post-transplant mortality after adoption of the MELD-based allocation system, a change that closely correlated with transplanting candidates with higher MELD scores [6], [7]. For example, in 2009, Weismüller et al demonstrated a 10% increase in three-month mortality at their transplant center in Germany after the adoption of MELD-based allocation as a result of pre-transplant factors [7]. However, to date only single-center studies have evaluated the impact on short-term mortality, while larger studies have focused on long-term post-transplant mortality, defined as over one-year, which is less likely to be impacted by severity of illness and the MELD score at the time of transplantation [8], [9]. In addition, most of these efforts have not included other variables potentially associated with post-transplant mortality such as hospitalization status and variables linked to ICU management. Furthermore, earlier publications may not fully reflect the current state of organ allocation and transplantation, in which patients are sicker, have more co-morbidities, and have higher MELD scores at transplantation [9].

Changes in allocation policies have also provided additional prioritization through the use of exception points for candidates with other complications of end-stage liver disease that may increase the need for hospitalization or ICU care. Moreover, the decision to transplant patients from the hospital or ICU remains center-based both in the US and in Europe. The potential impact of transplanting high MELD patients in an ICU on post-transplant outcomes has not been fully examined, except in small single-center studies [8]. In addition, the interaction between MELD score and hospitalization status may not only impact those with high MELD scores, but also those with low MELD scores whose severity of illness is not captured by the MELD score. With these issues in mind, our goals were to: 1) evaluate the impact of pre-transplant MELD score and hospitalization status on short-term post-transplant mortality; and 2) the interaction of these two variables.

Section snippets

Study population

All analyses were based on Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) data from February 27, 2002 through June 4, 2014. All adults (⩾18 years of age) initial single-organ transplant recipients prior to June 1, 2013 were included in order to evaluate outcomes prior to the implementation of the Share 35 policy on June 18, 2013, and to allow for ascertainment of outcomes among all transplant recipients. We excluded re-transplant and multi-organ

Results

There were 50,838 transplants initial liver transplant recipients during the study period. Of these 4095 (8.1%) were in an ICU prior to transplantation, and 5295 (10.4%) had a laboratory MELD score at transplantation ⩾35 (Table 1). Pre-transplant laboratory MELD score ranged from six to 40. In the study population, 12,992 (25.6%) were transplanted with HCC exception points. With regards to other factors hypothesized to be associated with early post-transplant mortality, 3223 (6.3%) patients

Discussion

In this analysis of liver transplant recipients in the US over an 11-year period, hospitalization status modified the risk of early post-transplant mortality for a given MELD score, with markedly increased risks of early post-transplant mortality in patients transplanted from an ICU. This finding is novel as the interaction between ICU status and MELD score has never been explored as a primary exposure. The influence of hospitalization status, specifically being in an ICU prior to

Financial support

David Goldberg: NIH K08 DK098272. This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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Research ArticleEarly post-transplant survival: Interaction of MELD score and hospitalization status

Background & Aims

Methods

Results

Discussion

Graphical abstract

Introduction

Section snippets

Study population

Results

Discussion

Financial support

Conflict of interest

Gastroenterology

Am J Transplant

Am J Transplant

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Am J Transplant

Am J Transplant

Transplant Proc

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J Hepatol

Predicting survival after liver transplantation based on pre-transplant MELD score: a systematic review of the literature

PLoS One

Multicentric evaluation of model for end-stage liver disease-based allocation and survival after liver transplantation in Germany–limitations of the ‘sickest first’-concept

Transpl Int

The introduction of MELD-based organ allocation impacts 3-month survival after liver transplantation by influencing pretransplant patient characteristics

Transpl Int

The changing face of patients presenting for liver transplantation

Curr Opin Organ Transplant

Declining outcomes in simultaneous liver-kidney transplantation in the MELD era: ineffective usage of renal allografts

Transplantation

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit

Aliment Pharmacol Ther

Research Article
Early post-transplant survival: Interaction of MELD score and hospitalization status