Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival

Simon Johannes Gairing, Chiara Mangini, Lisa Zarantonello, Stefania Gioia, Elise Jonasson Nielsen, Sven Danneberg, Anna S. Lok, Philippe Sultanik, Peter Robert Galle, Joachim Labenz, Dominique Thabut, Jens Uwe Marquardt, Patricia P. Bloom, Mette Munk Lauridsen, Sara Montagnese, Silvia Nardelli, Christian Labenz*

*Corresponding author for this work

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Background and aims: Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. Methods: Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). Results: A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. Conclusions: This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.

Original languageEnglish
JournalJournal of Internal Medicine
Issue number3
Pages (from-to)331-345
Publication statusPublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.


  • animal naming test
  • covert hepatic encephalopathy
  • decompensated cirrhosis
  • psychometric hepatic encephalopathy score
  • Liver Cirrhosis/complications
  • Hepatic Encephalopathy/complications
  • Europe
  • Humans
  • Psychometrics


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