Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.
Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.
The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.
Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.
The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).
The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.
Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”
The investigators reported having no external funding sources or conflicts of interest.
SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: .