Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation

Abstract

The prioritization of liver transplantation (LT) for patients with end-stage liver disease uses the Model for End-Stage Liver Disease (MELD), which attempts to identify the sickest patients and thereby those who are in greatest need for LT. Hepatic encephalopathy (HE) is not included in MELD, and severity of liver disease and risk of wait-list removal or wait-list death may be underestimated by MELD in patients with HE. Using United Network for Organ Sharing registry data, we evaluated the impact of HE on 90-day wait-list survival among adult LT wait-list registrants in the United States from 2003 to 2012. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and MELD. There were 84,947 new LT wait-list registrants during the study period; 36.8% had no HE, 57.4% had grade 1-2 HE, and 5.9% had grade 3-4 HE. Ninety-day wait-list mortality was significantly higher among patients with grade 3-4 HE compared with patients with grade 1-2 HE or no HE (24.4% versus 6.8% versus 3.5%; P < 0.001). When stratified by MELD, patients with grade 3-4 HE had 90-day wait-list mortality similar to that of nonencephalopathic patients with MELD scores 6-7 points higher. With the multivariate Cox proportional hazards model, patients with grade 3-4 HE had 66% greater risk of 90-day mortality than patients without HE (hazard ratio = 1.66, 95% CI = 1.45-1.90; P < 0.001). The inclusion of HE severity in MELD improved the area under receiver operating curve for predicting 90-day wait-list survival from 0.6508 to 0.6863. In conclusion, grade 3-4 HE at time of wait-list registration significantly increases 90-day wait-list mortality independent of MELD score. Incorporating HE in the assessment of LT priority may improve prognostication of liver disease severity and prioritization for LT.