Eye movement analysis detects early neurological alterations in cirrhotic patients classified as not having minimal hepatic encephalopathy by the Psychometric Hepatic Encephalopathy Score
Cirrhotic patients classified by the Psychometric Hepatic Encephalopathy Score (PHES) as without minimal hepatic encephalopathy (MHE) may present subtle cognitive alterations which could be detected by eye movement analysis. The aims were to develop a score for detecting early cognitive alterations in cirrhotic patients using specific psychometric tests and to identify which eye movement parameters could be used to detect them. A total of 118 cirrhotic patients (32 with MHE and 86 without MHE, according to PHES) and 35 healthy controls underwent psychometric assessment and eye movement testing by video-oculography. Forty-six patients without MHE (53.5%) showed impaired cognitive performance and were classified as having early cognitive impairment (early-MHE) using a novel score based on the most affected variables from several psychometric tests. This score was developed using historical cohorts of 519 cirrhotic patients and 74 age-matched healthy controls, and the optimal set of parameters included were from d2, Oral Symbol Digit Modalities, and Stroop tests. Early-MHE patients showed poorer cognitive performance and alterations in eye movement tests, particularly in antisaccade and fixation tasks. These abnormalities were more pronounced in MHE patients, suggesting a continuum of cognitive dysfunction from patients without detectable impairment by PHES to those with MHE. Eye movement variables with the highest predictive value for detecting mild cognitive alterations (early-MHE + MHE) were obtained from horizontal and vertical antisaccade tasks and fixation tests. Multivariate analysis grouping by eye movement task showed that a model including variables from the horizontal antisaccade test achieved the best predictive performance, with AUROC of 0.803 (95% CI: 0.711-0.896; p < 0.0001), 66.7% sensitivity, and 90.6% specificity at a relative-risk cutoff of 65.66%. Eye movement analysis is a rapid, objective, and non-invasive tool for detecting subtle neurological alterations in cirrhotic patients. This approach may facilitate earlier identification of cognitive impairment and support timely clinical intervention.
Authors
- Juan Gallego (ORCID: https://orcid.org/0000-0003-4368-5284)
- Amparo Urios (ORCID: https://orcid.org/0000-0003-2699-7040)
- Alessandra Fiorillo (ORCID: https://orcid.org/0000-0002-2125-8241)
- Carmina Montoliú (ORCID: https://orcid.org/0000-0002-4740-4788)
- Franc Casanova‐Ferrer (ORCID: https://orcid.org/0000-0001-7427-1987)
- Teresa San‐Miguel (ORCID: https://orcid.org/0000-0003-1892-6285)
- Javier Megías (ORCID: https://orcid.org/0000-0002-1457-0763)
- Lucía Durbán
- Montserrat Alcahuz-Griñán
- Adrià López‐Gramaje (ORCID: https://orcid.org/0009-0007-3784-8637)
- Elena Kosenko
- Danna Campos
- Cecilia E. Garcia-Cena (ORCID: https://orcid.org/0000-0002-1067-0564)
Institutions
- Universitat de València (ES)
- Institute of Theoretical and Experimental Biophysics (RU)
- Hospital Clínico Universitario de Valencia (ES)
- Hospital Arnau de Vilanova (ES)
- Centre for Automation and Robotics (ES)
- INCLIVA Health Research Institute (ES)
- Universidad Politécnica de Madrid (ES)
Publication Details
- Journal
- PLoS ONE
- Published
- 2026-09-15
- DOI
- https://doi.org/10.1371/journal.pone.0358353
- Primary Topic
- Liver Disease and Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Generalitat Valenciana
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agència Valenciana de la Innovació