title: The impact of pretransplant hepatic encephalopathy on survival following liver transplantation.
abstract: Hepatic encephalopathy (HE) is a surrogate marker of liver disease severity, and more severe HE is associated with higher mortality among patients with chronic liver disease. However, whether severity of HE at the time of liver transplantation (LT) directly impacts post-LT survival or whether this suspected mortality linkage is due to more severe liver disease and subsequently higher rates of post-LT infection is not well defined. Using population-based data from the 2003 to 2013 United Network for Organ Sharing registry, we evaluated the impact of HE at the time of LT on post-LT survival among adults in the United States. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and Model for End-Stage Liver Disease score and was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. From 2003 to 2013, 59,937 patients underwent LT (36.1%, no HE; 53.8%, grade 1-2 HE; 10.2%, grade 3-4 HE). Compared to no HE, patients with grade 3-4 HE had significantly lower overall post-LT survival (1-year, 82.5% versus 90.3%; P < 0.001; 5-year, 69.1% versus 74.4%; P < 0.001). On multivariate regression, grade 3-4 HE was independently associated with lower overall post-LT survival (HR, 1.27; 95% CI, 1.17-1.39; P < 0.001). However, the increased mortality associated with HE is observed primarily within the first year following LT and was a reflection of higher rates of infection-related deaths among patients with more severe HE. In conclusion, grade 3-4 HE at the time of LT is associated with lower post-LT survival, with a proposed direct or indirect association of more severe HE before LT with increased rates of post-LT infections. Increased awareness and vigilance toward treating HE before LT and more aggressive monitoring and treatment for infections in the perioperative setting may improve LT outcomes.
authors.affiliation: Division of Gastroenterology and Hepatology, Highland Hospital, Oakland, CA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wong
authors.affiliation: Department of Medicine, Alameda Health System, Highland Hospital, Oakland, CA.
authors.forename: Maria
authors.initials: M
authors.lastname: Aguilar
authors.affiliation: Hepatitis B Foundation, Doylestown, PA.|Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.|Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.
authors.forename: Ramsey
authors.initials: R
authors.lastname: Cheung
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D058625:End Stage Liver Disease / Q000601:surgery; D005260:Female; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000601:surgery*; D006801:Humans; D019934:International Normalized Ratio; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
chemical_list: D015415:Biomarkers