title: Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.
abstract: OBJECTIVE
  In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE).
  
  
  METHODS
  Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol, block design, and number connection [NCT-A and B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and first minus second halves (DeltaL(1-2)) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotic patients with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE.
  
  
  RESULTS
  In study A (226 cirrhotic patients), 54 had experienced OHE, 120 had minimal HE, and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotic patients were cognitively impaired, based on results from all tests. Learning of response inhibition (DeltaL(1-2) > or =1) was evident in patients with minimal HE and no minimal HE but was lost after OHE. In study B (50 additional patients who developed > or =1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r = 0.5, P = .0001), digit symbol test (r = -0.39, P = .002), and number connection test-B (r = 0.33, P = .04). In the prospective study (59 cirrhotic patients without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs 18 after, P = .0003), and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing.
  
  
  CONCLUSIONS
  In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia 23249, USA. jsbajaj@vcu.edu
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
authors.forename: Christine M
authors.initials: CM
authors.lastname: Schubert
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Gibson
authors.forename: Allyne
authors.initials: A
authors.lastname: Topaz
authors.forename: Kia
authors.initials: K
authors.lastname: Saeian
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hafeezullah
authors.forename: Debulon E
authors.initials: DE
authors.lastname: Bell
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Velimir
authors.initials: V
authors.lastname: Luketic
authors.forename: Melanie B
authors.initials: MB
authors.lastname: White
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D006501:Hepatic Encephalopathy / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D011594:Psychometrics