Two studies examine whether sodium levels can be used to predict mortality while waiting for and following transplant.
The most appropriate system for organ allocation for liver transplants is a subject of continuing debate. In the U.S. the Model for End-Stage Liver Disease (MELD) was introduced in 2002 as a way of prioritizing those with the highest risk of mortality and since that time waiting list mortality and waiting times have decreased with no negative impact on post-transplant survival.
The MELD score is based on objective and readily available variables, but in recent years many investigators have suggested adding additional factors to improve MELD's prognostic accuracy.
Hyponatremia (low sodium levels in the blood) is a strong predictor of wait-list mortality, but it has also been associated with worse post-transplant outcomes. Two new studies examined whether incorporating sodium levels into the MELD model is a valid approach to predicting outcomes for patients with severe liver disease.
The results of these studies appear in the August 2007 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS).
In the first study, researchers led by Angelo Luca of the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione in Palermo, Italy and Bernhard Angermayr of the Medical University of Vienna, Austria analyzed the records of 310 patients who underwent placement of a transjugular intrahepatic portosystemic shunt (TIPS) between 1999 and March 2005 at two European centers. They developed an integrated MELD (iMELD) model that incorporated both sodium levels and age, and tested it on 451 patients with cirrhosis who were on the waiting list for a liver transplant.
The results showed that both sodium levels and age are accurate predictors of prognosis, independent of the MELD score. The authors note that both sodium levels and age are objective, reliable, and readily available variables that may be useful in defining the priority of liver allocation as part of the iMELD model. "However, the inclusion of age into the iMELD might raise some ethical issues in this set of patients also because conflicting data exist on the risk of postoperative death in elderly liver transplant recipients," they conclude.
In another study, researchers led by M.F. Dawwas, of Cambridge University Hospitals NHS Foundation Trust, in Cambridge, UK, examined sodium levels in 5,152 patients in the UK and Ireland who underwent a liver transplant between 1994 and 2005. They found that the blood level of sodium measured immediately prior to transplant was an independent predictor of mortality following transplant. "Although the detrimental impact of both severe recipient hyponatraemia and hypernatraemia on post-transplant survival was confined to the first 90 days, they also had deleterious effects on the frequency of postoperative complications, functional status and resource utilization even among those who survived this period," the authors state.
They note that the reduced survival following transplant in patients with severe hyponatremia strongly suggests the importance of correcting sodium levels before surgery, although the question of whether bringing sodium levels into the normal range will improve transplant outcome requires further study. In addition, they found that patients with high sodium levels (which comprised a very small percentage) fared the worst, a finding that had not been previously published. The authors note that severe hyponatremia has a greater impact on wait-list mortality than post-transplant mortality, and conclude that "a liver allocation scheme prioritizing organs to hyponatraemic recipients might be likely to maximize survival benefit from the procedure."
In an accompanying editorial in the same issue, Scott W. Biggins of the University of California San Francisco in San Francisco, CA, notes that carefully applying models that predict mortality after transplant is a promising tool in further optimizing liver allocation. "The articles by Luca et al and Dawwas et al solidify the importance of [Na] as predictor of urgency for, and risk from, LTx [liver transplant] and fuel the debate over how to apply these risk assessments to rational improvements in liver graft allocation," he states. Regarding the question raised in the Luca study of whether a transplant candidate's age should be used for organ allocation, the author notes that as donor quality and post-transplant mortality risk models improve, a system that matches specific donor and recipient characteristics may improve the usefulness of liver transplants.
He notes that the Dawwas study presents new data important in balancing the urgency for transplant with post-transplant outcomes. "If incorporating [Na] into an allocation model could better predict severity of illness then perhaps hyponatremic patients would undergo transplant before their clinical state adversely impacted their post transplant outcome," he states. "The onus is on the transplant community to continuously refine the allocation system such that livers are targeted to patients who need them most without sacrificing the overall utility of this limited resource to society," he concludes.
"An Integrated MELD Model Including Serum Sodium and Age Improves the Prediction of Early Mortality in Patients with Cirrhosis," Angelo Luca, Berhard Angermayr, Guido Bertolini, Franz Koenig, Giovanni Vizzini, Martin Ploner, Markus Peck-Radosavljevic, Bruno Gridelli, Jami Bosch, Liver Transplantation; August 2007; (DOI: 10.1002/lt.21197).
"The Impact of Serum Sodium Concentration on Mortality After Liver Transplantation: A Cohort Multicenter Study," M.F. Dawwas, J.D. Lewsey, J.M. Neuberger, A.E. Gimson, Liver Transplantation; August 2007; (DOI: 10.1002/lt.21154).
"Beyond the Numbers: Rational and Ethical Application of Outcome Models for Organ Allocation in Liver Transplantation," Scott W. Biggins, Liver Transplantation; August 2007; (DOI: 10.1002/lt. 21210).
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