Author information
1Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
2Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
3Department of Medicine, University of Padova, Padova, Italy.
4Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
5Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark.
6Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany.
7Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
8Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Sorbonne Université, Paris, France.
9Department of Medicine, Diakonie Hospital Jung-Stilling, Siegen, Germany.
10Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Abstract
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.