Liver allocation based on model for end-stage liver disease-sodium (MELD-Na) score improved waitlist outcomes and provided significant benefit to patients with hyponatremia, researchers report in the November issue of Gastroenterology. However, there are discrepancies in transplantation survival benefit, so current rules for liver allocation might require revision, the authors state.
The MELD score had been used to allocate deceased donor liver grafts in the United States since 2002. Based on laboratory data, it provides an estimate of how urgently patients on the transplant waitlist need a liver—patients with higher scores have priority for liver transplantation.
Hyponatremia is an independent prognostic factor in patients with cirrhosis that was not included in the original MELD score calculation. Researchers therefore developed a modified scoring system to further decrease waitlist mortality that incorporated serum sodium concentration into the MELD equation (MELD-Na). This MELD-Na score was officially implemented for liver graft allocation in January 2016. The Share 35 rule offers livers to local and regional patients on the waitlist with MELD (and MELD-Na) scores of at least 35.
To determine the effects of the liver allocation based on MELD-Na score, Shunji Nagai et al compared waitlist outcomes and post-transplantation outcomes between the MELD and MELD-Na periods after Share 35 was implemented. They also evaluated the survival benefit of LT in the MELD-Na period.
The authors examined 2 groups of patients in the United Network for Organ Sharing registry. The MELD-period group comprised 18,850 patients who were registered as transplant candidates from June 18, 2013 through January 10, 2016 and the MELD-Na period group comprised 14,512 patients who were registered from January 11, 2016 through September 30, 2017. Nagai et al compared waitlist and post-transplantation outcomes and association with serum sodium concentrations between groups.
Although mild, moderate, and severe hyponatremia (130–134, 125–129, and below 125 mmol/L) were independent risk factors for waitlist mortality in the MELD period, risk decreased in the MELD-Na period.
Nagai et al performed propensity score matching for waitlist patients between the MELD and MELD-Na period groups to validate their findings; 14,244 waitlisted patients were selected from each group. Compared with the MELD period group, a lower proportion of patients in the MELD-Na period died within 90 days on the waitlist (8.1% vs 10.5% for MELD period) and a higher proportion received a liver transplantat (34.8% vs 30.0% in the MELD period, see figure). When the authors included propensity scores in a risk adjustment model, the hazard ratios of 90-day waitlist mortality and transplantation probability were 0.750 and 1.186, respectively, in the MELD-Na period.
In the MELD period, the risks of 90-day waitlist mortality in patients with mild, moderate, and severe hyponatremia were 1.354-fold, 1.762-fold, and 2.656-fold those of patients normal sodium levels. This effect decreased significantly in the MELD-Na period, to 1.092-fold, 1.271-fold, and 1.374-fold, respectively.
The overall waitlist mortality rates were 169.2 and 170.7 deaths per 1000 patient-years in the MELD-Na and MELD periods, respectively. The mortalities of in transplant recipients with 1-year follow-up were 114.1 and 98.3 deaths per 1000 patient-years in the MELD-Na and MELD periods, respectively.
The adjusted survival benefit of transplant recipients vs patients placed on the waitlist in the same score categories was definitive for patients with MELD-Na scores of 21–23 in the MELD-Na era (HR 0.336) compared with MELD scores of 15–17 in the MELD era (HR 0.365).
Hyponatremia determines MELD-Na scores, which might benefit hyponatremic patients with a MELD score that does not meet the cutoff for liver regional share programs (Share15 or Share35). Patients who had an initial and final MELD score lower than 15 but a MELD-Na score of at least 15 had a significantly greater likelihood of transplantation within 90 days in the MELD-Na period (26.1%) vs 12.7% in the MELD period, and they had significantly lower 90-day waitlist mortality in the MELD-Na period (1.9%) vs 10.6% in the MELD period.
Nagai et al acknowledge that the effective therapies for HCV infection developed probably improved waitlist outcomes. However, a subgroup analysis of HCV and non-HCV groups showed that the improvement in waitlist outcomes was greater among patients without HCV infection, compared to those HCV infection.
The effects of the MELD-Na score were less pronounced in patients with higher scores. The authors believe this was because the additional points added for hyponatremia are smaller in higher MELD score groups. Patients whose MELD-Na score was increased by hyponatremia to above 35 did benefit with the MELD-Na period, but the benefit observed was less obvious than in patients in lower score categories.
Nagai et al conclude that liver allocation based on the MELD-Na score has decreased waitlist mortality. Patients with hyponatremia and low MELD benefit from MELD-Na based allocation and the Share 15 rule, but the effects are less pronounced in patients with higher scores. The survival benefit of liver transplatation has shifted toward patients with higher scores in the MELD-Na period. The authors state that liver allocation rules such as Share 15 and Share 35 should be revised to fulfill the Final Rule under the MELD-Na based allocation.