Role of MRI in Detection of Minimal Hepatic Encephalopathy

• Conditions: Liver Cirrhoses; Hepatic Encephalopathy
• Interventions: Diagnostic Test: Magnetic Resonance Imaging

• Registration Number: NCT04131205
• Lead Sponsor: University Medical Centre Ljubljana

Brief Summary

Introduction Liver cirrhosis (LC) is irreversible fibrosis of the liver (1) and it remains a public health problem. One of the complications of the cirrhosis is hepatic encephalopathy (HE) which is defined as brain dysfunction caused by liver insufficiency. Pathophysiological mechanisms of HE are complex and multifactorial. Recognition of beginning stages of HE, such as minimal HE (mHE) is of most importance.

Objectives and originality of the project Diagnosis of mHE can be challenging, time-consuming and, at least to some extent, subjective. This project will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique. With advanced magnetic resonance (MR) techniques, in-vivo detection of intracellular water content, estimation pH and metabolites levels with millimolar concentrations can be easily performed. This will offer to explore possible pathophysiological mechanisms of HE and to evaluate the results from previous, studies that were mainly performed on animal models or cell cultures.

By our best knowledge, multimodal MR approach as the investigators propose in this application has not been yet performed. The investigators will use advanced MR techniques which are currently not available in the clinical setting and require multicenter collaboration.

Methods The investigators will include 10-20 patients of both genders with hyperammonemia and mHE and 10-20 patients of both genders with HE. Diagnosis of HE will be made based on results of validated neuropsychiatric test. Age-matched and gender-matched control group with no gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the blood. Patients with mHE/HE will be included from outpatient clinic of the Department of gastroenterology, University Medical Centre (UMC) Ljubljana. Healthy controls (HC) will be invited to join via internet advertisement. Contraindications for HC will include gastrointestinal (emphasis on liver disease), neurological or psychiatric complaints. Grade of mHE/HE will be classified according to West-Haven (WH) classification. Patients with different degree of liver cirrhosis, which will be scored with the Child-Pugh (CP) score, and with no contraindications for MR (e.g. presence of metal in body) will be included. Blood levels of liver enzymes and ammonia will be measured in all participants. MR scanning will include: T1- and T2-weighted MR, MRS (MEGA-PRESS and PRESS) in two voxels: striatum and cerebellum. Location will be double-checked by voxel position screenshots. Analysis, with voxel-positioning error compensation will be performed in Gannet (www.gabamrs.com). Moreover, high resolution diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM) will be performed in brain as well. Liver QSM will be executed to assess iron load.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-01
• Status Verified: 2019-10
• Study First Submitted: 2019-10-15
• Study First Submitted QC: 2019-10-16
• Last Update Submitted: 2019-10-16
• Study First Posted: 2019-10-18
• Last Update Posted: 2019-10-18
• Primary Completion: 2023-06-01
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Known liver disease/cirrhosis

Exclusion Criteria

• Pregnancy, non compatible material with MRI

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Minimal Hepatic Encephalopathy	Magnetic Resonance Imaging	Patients with hyperammonemia and minimal hepatic encephalopathy
Control	Magnetic Resonance Imaging	Healthy controls

Primary Outcome Measures

Name	Time	Method
Structural and Functional Changes in Brain Structures with Magnetic Resonance Imaging	2 hours	GABA levels and other neurotransmitters with respect to the tissue water signal and corrected for tissue composition.

Trial Locations

Locations (1)

Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana; 🇸🇮 Ljubljana, Slovenia