title: Hepatic Encephalopathy Is Associated with Persistent Learning Impairments Despite Adequate Medical Treatment: A Multicenter, International Study.
abstract: Hepatic encephalopathy (HE) is considered reversible regarding mental status but may not be cognitively in single-center studies.
  
  
  
  To evaluate persistence of learning impairment in prior HE compared to those who never experienced HE (no-HE) in a multicenter study.
  
  
  
  A total of 174 outpatient cirrhotics from three centers (94 Virginia, 30 Ohio, and 50 Rome; 36 prior HE) underwent psychometric hepatic encephalopathy score (PHES) and inhibitory control (ICT) testing at baseline and then at least 7 days apart. ICT learning (change in 2nd half lures compared to 1st half) was compared between patient groups at both visits. Change in the PHES individual sub-tests and total score between visits was compared in both groups. US versus Italian trends were also analyzed.
  
  
  
  HE patients had worse PHES and ICT results compared to no-HE patients at baseline. Significant improvement (1st half 7.1 vs. 2nd half 6.2, p < 0.0001) was observed in no-HE, but not in HE (1st half 7.9 vs. 2nd half 7.8, p = 0.1) at baseline. At retesting (median 20 days later), no-HE patients continued with significant learning (1st half 6.0 vs. 2nd half 5.4, p < 0.0001), while HE patients again did not improve (1st half 7.8 vs. 2nd half 6.9, p = 0.37). Between visits, no-HE patients improved significantly on four PHES sub-tests and overall score, while HE patients only improved on two sub-tests with similar overall PHES score. Trends were similar between US and Italian subjects.
  
  
  
  In this multicenter study, prior HE patients showed persistent significant learning impairment compared to those without prior HE, despite adequate medical therapy. This persistent change should increase efforts to reduce the first HE episode.
authors.affiliation: Division of Gastroenterology, Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nardelli
authors.affiliation: Division of Gastroenterology, Metrohealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Sanath
authors.initials: S
authors.lastname: Allampati
authors.affiliation: Division of Gastroenterology, Sapienza University of Rome, Rome, Italy.
authors.forename: Oliviero
authors.initials: O
authors.lastname: Riggio
authors.affiliation: Division of Gastroenterology, Metrohealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Mullen
authors.affiliation: Division of Gastroenterology, Metrohealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Prakash
authors.affiliation: Division of Gastroenterology, Sapienza University of Rome, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gioia
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Unser
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, 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, VA, 23249, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Fagan
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Gavis
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA. jsbajaj@vcu.edu.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
mesh_terms: D000368:Aged; D003071:Cognition; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000523:psychology; D006801:Humans; D007361:Intelligence Tests; D007558:Italy / Q000453:epidemiology; D007792:Lactulose / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D016743:Mental Competency; D008875:Middle Aged; D011594:Psychometrics / Q000379:methods; D014481:United States / Q000453:epidemiology
chemical_list: D005765:Gastrointestinal Agents; D007792:Lactulose
keywords: Cirrhosis; Inhibitory control test; Lactulose; Psychometric hepatic encephalopathy score; Rifaximin