Role of MRI in Detection of Minimal Hepatic Encephalopathy
NCT ID: NCT04131205
Last Updated: 2019-10-18
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
40 participants
Study Classification
OBSERVATIONAL
Study Start Date
2019-06-01
Study Completion Date
2023-06-01
Brief Summary
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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.
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.
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Detailed Description
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Conditions
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Liver Cirrhoses
Hepatic Encephalopathy
Study Design
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Observational Model Type
CASE_CONTROL
Study Time Perspective
PROSPECTIVE
Study Groups
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Minimal Hepatic Encephalopathy
Patients with hyperammonemia and minimal hepatic encephalopathy
Magnetic Resonance Imaging
Intervention Type
DIAGNOSTIC_TEST
We will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique
Control
Healthy controls
Magnetic Resonance Imaging
Intervention Type
DIAGNOSTIC_TEST
We will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique
Interventions
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Magnetic Resonance Imaging
We will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique
Intervention Type
DIAGNOSTIC_TEST
Other Intervention Names
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Ammonia Levels
Child Pugh Score
West-Haven grade of Hepatic Encephalopathy
Eligibility Criteria
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Inclusion Criteria
* Known liver disease/cirrhosis
Exclusion Criteria
* Pregnancy, non compatible material with MRI
Minimum Eligible Age
18 Years
Maximum Eligible Age
85 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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University of Ljubljana, Faculty of Medicine
OTHER
Sponsor Role
collaborator
Medical University of Graz
OTHER
Sponsor Role
collaborator
Johns Hopkins University
OTHER
Sponsor Role
collaborator
University Medical Centre Ljubljana
OTHER
Sponsor Role
lead
Responsible Party
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Sebastian Stefanovic, MD
Clinical Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Dusan Suput, M.D.
Role: STUDY_CHAIR
Medical Faculty of Ljubljana
Borut Stabuc, M.D.
Role: STUDY_CHAIR
Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana
Locations
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Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana
Ljubljana, , Slovenia
Site Status
RECRUITING
Countries
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Slovenia
Central Contacts
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Facility Contacts
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References
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American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available.
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Reference Type
BACKGROUND
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Reference Type
BACKGROUND
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Ge PS, Runyon BA. Treatment of Patients with Cirrhosis. N Engl J Med. 2016 Aug 25;375(8):767-77. doi: 10.1056/NEJMra1504367. No abstract available.
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Lee JH, Seo DW, Lee YS, Kim ST, Mun CW, Lim TH, Min YI, Suh DJ. Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve. Am J Gastroenterol. 1999 Aug;94(8):2206-13. doi: 10.1111/j.1572-0241.1999.01228.x.
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Mechtcheriakov S, Schocke M, Kugener A, Graziadei IW, Mattedi M, Hinterhuber H, Vogel W, Marksteiner J. Chemical shift magnetic resonance spectroscopy of cingulate grey matter in patients with minimal hepatic encephalopathy. Neuroradiology. 2005 Jan;47(1):27-34. doi: 10.1007/s00234-004-1298-8. Epub 2005 Jan 18.
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Miese F, Kircheis G, Wittsack HJ, Wenserski F, Hemker J, Modder U, Haussinger D, Cohnen M. 1H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy. AJNR Am J Neuroradiol. 2006 May;27(5):1019-26.
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Oeltzschner G, Butz M, Baumgarten TJ, Hoogenboom N, Wittsack HJ, Schnitzler A. Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes. Metab Brain Dis. 2015 Dec;30(6):1429-38. doi: 10.1007/s11011-015-9729-2. Epub 2015 Sep 11.
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Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357.
Reference Type
RESULT
Other Identifiers
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HepaticEncephalopathy
Identifier Type: -
Identifier Source: org_study_id
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