Evolution of hepatic encephalopathy over time: ecological data from a tertiary referral centre for hepatology



      Few data on hepatic encephalopathy (HE) over time are available, thus our aim was to study its evolution in patients with varying degree of HE on first assessment.


      Eighty-six patients with cirrhosis (age = 58 ± 11 years; males = 72) were evaluated 2–10 times for liver transplantation selection purposes, differential diagnosis or treatment optimization. The presence/severity of HE was assessed by clinical and neuropsychiatric indices [ Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalography (EEG)] and the severity of liver disease by the Model for End-Stage Liver Disease (MELD) score. Treatment was instituted/modified after each evaluation.


      Amongst 23 unimpaired patients, 56/6% remained unimpaired, 35/3% developed covert HE, 9/0% developed overt HE on second/third evaluation. Amongst 32 patients with covert HE, 25/10% became unimpaired, 44/19% remained covert, 31/13% developed overt HE. Finally, amongst 32 patients with overt HE, 19/16% became unimpaired, 25/13 % became covert and 56/25% remained overt. PHES results improved in patients with overt HE and EEG worsened over time (despite remaining normal) in unimpaired patients. In patients with multiple evaluations, HE evolution was manifold and difficult to predict.


      HE evolution over time is variable and largely dependent on HE history/management. These data support the concept that HE is an essentially reversible condition.



      HE (hepatic encephalopathy), MELD (Model for End-Stage Liver Disease), PHES (Psychometric Hepatic Encephalopathy Score), MPZS (mean PHES Z score), MDF (mean dominant frequency)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sherlock S.
        • Summerskill W.H.
        • White L.P.
        • et al.
        Portal- systemic encephalopathy; neurological complications of liver disease.
        Lancet. 1954; 267: 454-457
        • Parsons-Smith B.G.
        • Summerskill W.H.
        • Dawson A.M.
        • et al.
        The electroencephalograph in liver disease.
        Lancet. 1957; 273: 867-871
        • Rikkers L.
        • Jenko P.
        • Rudman D.
        • et al.
        Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism.
        Gastroenterology. 1978; 75: 462-469
        • Amodio P.
        • Montagnese S.
        • Gatta A.
        • et al.
        Characteristics of minimal hepatic encephalopathy.
        Met Brain Dis. 2004; 19: 253-267
        • Vilstrup H.
        • Amodio P.
        • Bajaj J.
        • et al.
        Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American association for the study of liver diseases and the European association for the study of the liver.
        Hepatology. 2014; 60: 715-735
        • Montagnese S.
        • Russo F.P.
        • Amodio P.
        • et al.
        Hepatic encephalopathy 2018: a clinical practice guideline by the Italian association for the study of the liver (AISF).
        Dig Liver Dis. 2019; 51: 190-205
        • Bustamante J.
        • Rimola A.
        • Ventura P.J.
        • et al.
        Prognostic significance of hepatic encephalopathy in patients with cirrhosis.
        J Hepatol. 1999; 30: 890-895
        • Jepsen P.
        • Ott P.
        • Andersen P.K.
        • et al.
        Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study.
        Hepatology. 2010; 51: 1675-1682
        • Dhiman R.K.
        • Kurmi R.
        • Thumburu K.K.
        • et al.
        Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver.
        Dig Dis Sci. 2010; 55: 2381-2390
        • Bianchi G.
        • Giovagnoli M.
        • Sasdelli A.S.
        • et al.
        Hepatic encephalopathy and health-related quality of life.
        Clin Liver Dis. 2012; 16: 159-170
        • Ochoa-Sanchez R.
        • Rose C.F.
        Pathogenesis of hepatic encephalopathy in chronic liver disease.
        J Clin Exp Hepatol. 2018; 8: 262-271
        • Montagnese S.
        • Bajaj J.S.
        Impact of hepatic encephalopathy in cirrhosis on quality-of-life issues.
        Drugs. 2019; 79 (11–6.l)
        • Sharma B.C.
        • Sharma P.
        • Agrawal A.
        • et al.
        Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo.
        Gastroenterology. 2009; 137: 885-891
        • Hartmann I.J.
        • Groeneweg M.
        • Quero J.C.
        • et al.
        The prognostic significance of subclinical hepatic encephalopathy.
        Am J Gastroenterol. 2000; 95: 2029-2034
        • Romero-Gómez M.
        • Boza F.
        • García-Valdecasas M.S.
        • et al.
        Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy.
        Am J Gastroenterol. 2001; 96: 2718-2723
        • Patidar K.R.
        • Thacker L.R.
        • Wade J.B.
        • et al.
        Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization.
        Am J Gastroenterol. 2014; 109: 1757-1763
        • Flud C.R.
        • Duarte-Rojo A.
        Prognostic implications of minimal/covert hepatic encephalopathy: large-scale validation cohort studies.
        J Clin Exp Hepatol. 2019; 9: 112-116
        • Bajaj J.S.
        • Schubert C.M.
        • Heuman D.M.
        • et al.
        Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.
        Gastroenterology. 2010; 138: 2332-2340
        • Riggio O.
        • Ridola L.
        • Pasquale C.
        • et al.
        Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy.
        Clin Gastroenterol Hepatol. 2011; 9: 181-183
        • Ferenci P.
        Hepatic encephalopathy.
        Gastroenterol Rep. 2017; 5: 138-147
        • Amodio P.
        • Montagnese S.
        • Mullen K.
        • et al.
        Where are we going? Translational research in hepatic encephalopathy.
        Metab Brain Dis. 2016; 31: 1231-1237
        • Campagna F.
        • Montagnese S.
        • Schiff S.
        • et al.
        Cognitive impairment and electroencephalographic alterations before and after liver transplantation: what is reversible?.
        Liver Transpl. 2014; 20: 977-986
        • Atluri D.K.
        • Asgeri M.
        • Mullen K.D.
        Reversibility of hepatic encephalopathy after liver transplantation.
        Metab Brain Dis. 2010; 25: 111-113
        • Tan H.H.
        • Lee G.H.
        • Thia K.T.
        • et al.
        Minimal hepatic encephalopathy runs a fluctuating course: results from a three-year prospective cohort follow-up study.
        Singap Med J. 2009; 50: 255-260
        • Weissenborn K.
        • Ennen J.C.
        • Schomerus H.
        • et al.
        Neuropsychological characterization of hepatic encephalopathy.
        J Hepatol. 2001; 34: 768-773
        • Amodio P.
        • Campagna F.
        • Olianas S.
        • et al.
        Detection of minimal hepatic encephalopathy: normalization and optimization of the psychometric hepatic encephalopathy score. a neuropsychologi-cal and quantified EEG study.
        Hepatology. 2008; 49: 346-353
        • Campagna F.
        • Montagnese S.
        • Ridola L.
        • et al.
        The animal naming test: an easy tool for the assessment of hepatic encephalopathy.
        Hepatology. 2017; 66: 198-208
        • Van der Rijt C.C.
        • Schalm S.W.
        • De Groot G.H.
        • et al.
        Objective measurement of hepatic encephalopathy by means of automated EEG analysis.
        Electroencephalogr Clin Neurophysiol. 1984; 57: 423-426
        • Amodio P.
        • Marchetti P.
        • Del Piccolo F.
        • et al.
        Spectral versus visual EEG analysis in mild hepatic encephalopathy.
        Clin Neurophysiol. 1999; 110: 1334-1344
        • Mangini C.
        • Montagnese S.
        New therapies of liver diseases: hepatic encephalopathy.
        J Clin Med. 2021; 18: 40-50
        • Cordoba J.
        • Ventura-Cots M.
        • Simón-Talero M.
        • et al.
        CANONIC study investigators of EASL-CLIF consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF).
        J Hepatol. 2014; 60: 275-281
        • Formentin C.
        • Zarantonello L.
        • Mangini C.
        • et al.
        Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE).
        Liver Int. 2021; 41: 1070-1082