Development of a Cognitive Tool for Rapid and Reliable Screening of Minimal Hepatic Encephalopathy: Pilot Study (BLOCK-HE)

The aim of this project is to evaluate the sensitivity and specificity of a cognitive test toward the presence of minimal hepatic encephalopathy (MHE). MHE is a neurological complication due to hepatic dysfunction and/or the presence of porto-systemic shunts defined by the presence of neurocognitive impairments (NI). Other factors of brain injury may cause NI independently from the liver condition making the differential diagnosis difficult using available cognitive tests (ANT Animal Naming Test, PHES Psychometric Hepatic Encephalopathy Score, CFF Critical Flicker Frequency test). The cognitive test evaluated in this project is a construction task using construction blocks, allowing the evaluation of psychomotor speed, executive functions, attention, and episodic memory. The measures will be compared to other cognitive tests validated for the evaluation of the targeted cognitive functions (PHES, Mesulam Cancelling task, Rey-Osterrieth complex figure, Free and Cued Selective Reminding Test) and cognitive tests validated for the diagnosis of MHE (PHES, ANT, CFF). The diagnosis of MHE is based on an adjudication committee including a multimodal assessment of MHE (brain MRI with spectroscopy, EEG, blood sample, neuropsychological assessment), allowing the evaluation of comorbidities such as other factors of brain injury.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Pathology (Fibrosis, Cirrhosis, Porto Systemic Shunts)
• Intervention / Treatment: Other: Cognitive test

Detailed Description

Hepatic encephalopathy (HE), corresponding to all the neurocognitive symptoms caused by liver damage and/or the presence of portosystemic shunts. HE can take several forms depending on its intensity, ranging from subtle neuropsychological abnormalities that are difficult to detect during a routine interview ("minimal" HE, MHE) to temporospatial disorientation and confusion that can lead to coma ( "overt" HE, OHE). MHE can significantly impair the quality of life of patients and caregivers; it is associated with a poorer prognosis of liver pathology and a significantly more frequent occurrence of OHE. Detection of MHE is complex, and involves the convergence of a large number of tests recognized as sensitive: venous ammonia level, electroencephalogram, MRI with spectroscopy, complete neuropsychological assessment. Today, there is no unanimously recognized Gold Standard.

The objective of this research project is to develop a cognitive test to detect HE sensitively and specifically, in order to detect HE.

To do this, the investigators will evaluate the qualities of a rapid and accessible test. It is a test made up of building blocks to assess psychomotor speed, attention, executive functions and episodic memory. If it proves sensitive and specific enough for the diagnosis of MHE, it could be disseminated and allow the screening of MHE.

To do this, the investigators will compare the block construction test to other neuropsychological examinations validated in the diagnosis of MHE (PHES: Psychometric Hepatic Encephalopathy Score, CFF: Critical Flicker Frequency test, ANT: Animal Naming Test). These examinations are reference cognitive tests in the diagnosis of MHE, but the results between these tests diverge and do not currently make it possible to replace all of the clinical examinations described above. The investigators will also compare the construction block test to cognitive tests validated for the evaluation of the targeted cognitive functions (ROCF Rey-Osterrieth complex figure, FCSRT Free and Cued Selective Reminding test, MCT Mesulam cancelling task). The diagnosis of MHE is based on an adjudication committee including a multimodal assessment of MHE (brain MRI with spectroscopy, EEG, blood sample, neuropsychological assessment), allowing the evaluation of comorbidities such as other factors of brain injury.

Main objective : to evaluate the sensitivity and specificity of the construction test to the presence of MHE.

Secondary objectives:

1. Comparison of screening qualities of the construction test to MHE diagnosis validated tests (PHES, CFF, ANT)
2. Evaluate the impact of the presence of comorbidities (factors of brain injury) in the results of the construction test.
3. Evaluate the psychometric qualities of the construction test compared to validated neuropsychological tests.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Lyès KHELOUFI; Phone Number: +33 01 84 82 74 83; Email: lyes.kheloufi@aphp.fr
• Study Contact Backup: Name: Nicolas WEISS, MD,PhD; Phone Number: +33 01 42 16 27 70; Email: nicolas.weiss@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Hepato-gastro-enterology department, Pitié Salpêtrière hospital
    • Contact: Lyès KHELOUFI; Phone Number: +33 01 84 82 74 83; Email: lyes.kheloufi@aphp.fr
    • Contact: Nicolas WEISS, MD,PhD; Phone Number: +33 01 42 16 27 70; Email: nicolas.weiss@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with liver cirrhosis or portosystemic shunts with suspicion of minimal hepatic encephalopathy

Description

Inclusion Criteria:

• Age between 18 and 70 years
• Hepatic pathology (fibrosis, cirrhosis, porto-systemic shunts)
• Evaluation at BLIPS clinic (neuropsychological assessment, MRI, EEG and blood sample with ammonia)

Exclusion Criteria:

• Opposition to participating in the study
• Not being affiliated with French healthcare system

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients; Population with chronic liver disease or the presence of portal-systemic shunts, attending the BLIPS day hospital	Other: Cognitive test; Cognitive test based on building blocks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
sensitivity and specificity of the construction test according to the diagnosis of MHE, after construction of a logistic model.	between day 0 and 14 from inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the sensitivities and specificities of the construction test compared to the MHE reference tests	Comparison of the sensitivities and specificities of the construction test compared to the MHE reference tests like: PHES (Psychometric Hepatic Encephalopathy Score), CFF (Critical Flicker Frequency test), ANT (Animal Naming Test)	Between day 0 and 14 from inclusion
Evaluate the sensitivity and specificity of the construction test for the diagnosis of hepatic encephalopathy, taking into account the presence of neurological comorbidities.		Between day 0 and 14 from inclusion
Correlation analysis between subsets of the construction test (planning, speed, selective attention, memory) with reference cognitive tests assessing these cognitive functions	Correlation analysis between subsets of the construction test (planning, speed, selective attention, memory) with reference cognitive tests assessing these cognitive functions like: ROCF (Rey-Osterrieth complex figure), FCSRT (Free and Cued Selective Reminding test), MCT (Mesulam cancelling task), PHES subtests (Psychometric Hepatic Encephalopathy Score)	Between day 0 and 14 from inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Nicolas WEISS, MD,PhD, Assistance Publique - Hôpitaux de Paris; Study Director: Dominique THABUT, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2026
• Primary Completion (Estimated): January 29, 2028
• Study Completion (Estimated): January 29, 2028

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: neurology; neuropsychology; Hepatic encephalopathy; hepatic failure; cognitive tools
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Fibrosis; Liver Failure; Hepatic Encephalopathy; Behavioral Disciplines and Activities; Psychological Tests; Neuropsychological Tests
• Other Study ID Numbers: APHP231310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No