title: Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization.
abstract: OBJECTIVE
  Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE.
  
  
  METHODS
  Outpatient cirrhotics without OHE were enrolled and were administered a standard paper-pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression.
  
  
  RESULTS
  A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0 ± 14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01-4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4-4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2-9.7) in the follow-up period.
  
  
  CONCLUSIONS
  Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Kavish R
authors.initials: KR
authors.lastname: Patidar
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Thacker
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Siddiqui
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Matherly
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Puri
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: White
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Noble
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Unser
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: HoChong
authors.initials: H
authors.lastname: Gilles
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D015996:Survival Rate