Model for End-Stage Liver Disease–Sodium Score: The Evolution in the Prioritization of Liver Transplantation

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Key points

  • The model for end-stage liver disease (MELD) -based allocation system implemented in 2002 was the first step toward prioritizing liver transplantation for the patients with the highest risk of mortality.

  • The incorporation of sodium to the MELD score has made the model stronger in predicting mortality among liver transplant candidates.

  • The current allocation system for patients with hepatocellular carcinoma still allows outcome disparity compared with patients without hepatocellular carcinoma.

Historical perspective: starting to regulate liver transplantation

It has been more than 50 years since Starzl and colleagues1 performed the first successful human liver transplantation (LT) in the United States. In the following years, LT gradually established its role as definitive therapy for patients with acute liver failure and end-stage liver disease, and later on for selected patients with hepatocellular carcinoma (HCC). Afterward, the limited availability of cadaveric organs became the main limiting factor for the wider use of LT. At the same time, the

The first improvement: creation of the UNOS status classification

Child and Turcotte2 described in 1964 the first classification system for the prediction of survival among patients with cirrhosis complicated by variceal bleeding undergoing portosystemic shunt surgery, which was based on 3 clinical variables: ascites, hepatic encephalopathy, and nutritional status, plus 2 laboratory values: serum bilirubin and albumin. This classification divided patients with cirrhosis into 3 categories, based on their mortality risk for major surgery. In 1973, Pugh and

Redefining priority for transplantation: the final rule

The 1997 UNOS status classification for transplant priority, although an improvement, was neglecting patients with decompensated cirrhosis who were not requiring ICU care. Several drawbacks were identified with the use of the CTP score, including the fact that relied on subjective data to assess the severity of hepatic encephalopathy and ascites. The most critical issue was the fact that within each status category the tiebreaker for priority was still time on the waiting list, rather than the

A mathematical formula help solving the liver allocation problem

The Mayo End-Stage Liver Disease model was originally derived from a cohort of patients with cirrhosis as a tool to predict short-term survival (3 months) after undergoing transjugular intrahepatic portosystemic shunt (TIPS).10 Its original name reflected the affiliation of the investigators that developed this mathematical model. The formula used for calculation required the addition of the logarithmic expression of 3 laboratory values: serum creatinine, bilirubin, and INR, which reflect the

Liver organ allocation improves with the meld implementation

Within 1 year after the MELD score was implemented, there was a 12% reduction in the number of new LT candidate registrations in the UNOS Database, mainly among candidates with MELD score less than 10.20 Likewise, there was a 10.2% increase in the rate of cadaveric LT, which was attributable to an increase in organ availability and also to the effect of MELD implementation, and the median time to transplantation was reduced by more than 200 days.21 Most notably, the use of the MELD score for

Improving the prediction of survival with adding sodium to the calculation

Hypervolemic hyponatremia is a complication of decompensated cirrhosis, characterized by a low serum sodium concentration in patients with an expanded extracellular volume, commonly with ascites. The pathophysiology of the hyponatremia is related to increased secretion of antidiuretic hormone (ADH), as a compensatory mechanism to the circulatory dysfunction present in cirrhosis. ADH causes impairment of solute-free water excretion in the renal collecting tube. Hyponatremia has long been

Addressing geographic disparities: distribution of organs

The MELD implementation had no significant effect on the geographic disparities regarding organ allocation, which were previously identified by the IOM report. The average MELD at time of transplantation is quite variable depending on the specific UNOS region.50 Similarly, within each UNOS region, there exists variability between the donor service areas (DSA) that conform a specific region. There is a 10-point range in average MELD score at time of transplantation, among different DSAs within

Model for end-stage liver disease exceptions: the case for hepatocellular carcinoma

The most significant limitation of the MELD score system has been its inability to properly prioritize for transplantation patients with the concomitant diagnosis of HCC. The candidates with HCC commonly have relatively low MELD scores at time of diagnosis, that underestimate their urgency for transplantation before progression of tumor beyond that amenable to LT.

At the same time of MELD implementation in 2002, an MELD exception system was also designed for patients carrying the diagnosis of

Model for end-stage liver disease exception: pulmonary complications of cirrhosis

OPTN/UNOS grants MELD exceptions to LT candidates with cirrhosis and pulmonary complications carrying a higher risk of mortality, not accounted for by the MELD formula. The 2 recognized pulmonary complications are hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). In the case of HPS, the presence of clinical evidence of pulmonary hypertension, documentation of intrapulmonary shunt, and a partial pressure of oxygen in arterial blood (Pao2) of ≤60 mm Hg are required for MELD

Other model for end-stage liver disease exceptions

Rare metabolic conditions, which benefit from LT, are also eligible for MELD exception by OPTN/UNOS, because intrinsic MELD would never increase due to the underlying disease, which has no effect on the intrinsic function of the liver. These conditions include familial amyloid polyneuropathy, cystic fibrosis, and primary hyperoxaluria. The requirement for MELD exception for each condition is disease specific and out of the scope of this review. The diagnosis of hilar cholangiocarcinoma could be

Summary

The criteria used for prioritization of LT in the United States have evolved over time. The concept of favoring LT for the patients with the highest risk of mortality due to liver disease has been the widely accepted criteria. The greatest change in the liver allocation system has been the adoption of the MELD scoring system as a surrogate marker of the severity of chronic liver disease. Following the implementation of MELD score for organ allocation by OPTN/UNOS, waiting time has lost

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