Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)
Primary Purpose
Nonalcoholic Steatohepatitis
Status
Completed
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Imaging diagnostic and biopsy
Sponsored by
About this trial
This is an interventional prevention trial for Nonalcoholic Steatohepatitis focused on measuring Magnetic resonance imager(MRI), Nonalcoholic fatty liver disease(NAFLD), Imaging diagnostic
Eligibility Criteria
Inclusion Criteria:
- Patients >19 years age
- Patients who had elevated aspartate transaminase(AST)/alanine transaminase(ALT) and fatty liver on abdominal ultrasonography
Patients who are clinically suspected to have nonalcoholic steatohepatitis(NASH)
- Clinically suspected nonalcoholic steatohepatitis(NASH): >40 years age, metabolic syndrome, fibrosis on transient elastography(TE, Fibroscan), or elevated Fibrosis-4(FIB-4), Aspartate aminotransferase-to-platelet ratio index(APRI), nonalcoholic fatty liver disease fibrosis score(NFS) on blood tests
- Patients who underwent (<6 months) or will undergo US-guided liver biopsy
Exclusion Criteria:
- Chronic liver disease other than nonalcoholic fatty liver disease(NAFLD) (chronic hepatitis B or C, autoimmune hepatitis, primary biliary sclerosis)
- Alcohol abuse (men, >140g/week; women, >70g/week)
- Fatty liver due to medication
- Contraindication to magnetic resonance imager(MRI)
- Hepatocellular carcinoma
- Pregnancy
Sites / Locations
- Korea University Guro Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Imaging diagnostic and biopsy
Arm Description
47 subjects who are suspected NASH from June 2016 to December 2017.
Outcomes
Primary Outcome Measures
Radiologic Diagnosis & Criteria of nonalcoholic steatohepatitis(NASH)
Development of non-invasive magnetic resonance imaging diagnostic model for NASH using linear regression analysis
Linear regression analysis using three magnetic resonance(MR) parameters 1) Fat signal fraction measured on MR spectroscopy (unit: %) 2) Liver stiffness measured on MR elastography (unit: kPa) 3) T1 relaxation time measured on T1 mapping (unit: msec) → Development of linear equation for NAFLD activity score (NAS) and Steatosis, Activity, Fibrosis (SAF) score
Fitting of observed values (NAS, SAF score) and predicted values (NAS, SAF score) → Obtaining R square (R2) (Unit: none)
Secondary Outcome Measures
Fat imaging : Fat signal fraction measured on magnetic resonance(MR) spectroscopy
* Fat signal fraction measured on magnetic resonance(MR) spectroscopy
high speed T2-corrected multi-echo (HISTO) MR spectroscopic technique
multiple short echo time : correction of T2 bias
long repetition time: correction of T1 bias
15 x 15 x 15-mm square-shaped region-of-interest(ROI) → Right hepatic lobe
3 times measurement → mean value was used as a representative value
unit: percentage (%)
Receiver operating characteristic (ROC) curve analysis for steatosis grade (0-3) → Obtaining cut-off values of each steatosis grade and area under the curve (AUC)
Fibrosis imaging(1) : Liver stiffness measured on magnetic resonance elastography(MRE)
* Magnetic resonance elastography(MRE)
60 Hz acoustic wave
Four slices were obtained for each magnetic resonance elastography(MRE) examination
Stiffness maps (elastograms) for each magnetic resonance elastography(MRE) slices were automatically generated
free-hand region-of-interest (ROI) on the right hepatic lobe
5 times measurement → mean value was used as a representative value
unit: kilopascal (kPa)
Receiver operating characteristic (ROC) curve analysis for fibrosis grade (0-4) → Obtaining cut-off values of each fibrosis grade and area under the curve (AUC)
Fibrosis imaging(2) : T1 relaxation time measured on T1 mapping
* T1 mapping
Shortened Modified Look Locker Inversion (shMOLLI) recovery sequence
Four slices were obtained for each T1 map
Oval-shaped region-of-interest (ROI) in the right hepatic lobe
5 times measurement → mean value was used as a representative value
unit: millisecond (msec)
Receiver operating characteristic (ROC) curve analysis for ballooning (0-2), lobular inflammation (0-3), fibrosis grade (0-4) → Obtaining cut-off values of each grade and area under the curve (AUC)
Histologic interpretation(1) : Nonalcoholic fatty liver disease activity score (NAS)
the sum of each histological component semiquantitatively evaluated as follows: steatosis (0-3), ballooning (0-2), and lobular inflammation (0-3)
NAS 0-2: not considered steatohepatitis
NAS 3-4: possible steatohepatitis 4/ NAS ≥5: definite steatohepatitis
Histologic interpretation(1) : Steatosis, Activity, Fibrosis (SAF) score
steatosis (0-3), ballooning degeneration (0-2), lobular inflammation (0-2), and fibrosis (0-4).
Nonalcoholic steatohepatitis(NASH): when steatosis is present and when both features of activity (ballooning and lobular inflammation) display at least grade 1
Unit: None
Full Information
NCT ID
NCT03375008
First Posted
November 22, 2017
Last Updated
May 14, 2019
Sponsor
Korea University Guro Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03375008
Brief Title
Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)
Official Title
Development of Non-invasive Magnetic Resonance Imaging Diagnostic Method for Nonalcoholic Steatohepatitis(NASH)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
September 8, 2016 (Actual)
Primary Completion Date
August 7, 2018 (Actual)
Study Completion Date
August 7, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Korea University Guro Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate feasibility of using multiparametric Magnetic resonance(MR) imaging to predict nonalcoholic steatohepatitis(NASH)
To develop non-invasive diagnosis tool using multiparametric Magnetic resonance(MR) imaging for nonalcoholic steatohepatitis(NASH)
Detailed Description
Nonalcoholic steatohepatitis(NASH) is a severe form of nonalcoholic fatty liver disease(NAFLD). The causes are known to be associated with metabolic diseases such as obesity, insulin resistance type 2 diabetes, and hypercholesterolemia. Histologically, it is characterized by steatosis, hepatocellular injury, and inflammation and fibrosis of the liver parenchyma. Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma(HCC) may develop even in patients without viral hepatitis, therefore there have been much interest and many researches in causation and diagnosis for nonalcoholic steatohepatitis(NASH).
Liver biopsy remains the gold standard for the diagnosis of nonalcoholic fatty liver disease(NAFLD) and is the only reliable method for differentiating nonalcoholic steatohepatitis(NASH) from simple steatosis. However, liver biopsy has several drawbacks, including invasiveness, potential complications such as excessive bleeding and death, sampling error, and inter- and intra-observer variability.
Magnetic resonance(MR) imaging has been used as a multiparametric imaging tool with which to evaluate steatosis by chemical shift imaging andm magnetic resonance(MR) spectroscopy, and fibrosis by magnetic resonance(MR) elastography and T1 mapping. To the best of our knowledge, there is no accurate imaging diagnostic tool for nonalcoholic steatohepatitis(NASH), therefore the investigators aimed to develop non-invasive imaging diagnostic model using multiparametric magnetic resonance imager(MRI).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis
Keywords
Magnetic resonance imager(MRI), Nonalcoholic fatty liver disease(NAFLD), Imaging diagnostic
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imaging diagnostic and biopsy
Arm Type
Experimental
Arm Description
47 subjects who are suspected NASH from June 2016 to December 2017.
Intervention Type
Diagnostic Test
Intervention Name(s)
Imaging diagnostic and biopsy
Intervention Description
Liver biopsy and MRI scan
Primary Outcome Measure Information:
Title
Radiologic Diagnosis & Criteria of nonalcoholic steatohepatitis(NASH)
Description
Development of non-invasive magnetic resonance imaging diagnostic model for NASH using linear regression analysis
Linear regression analysis using three magnetic resonance(MR) parameters 1) Fat signal fraction measured on MR spectroscopy (unit: %) 2) Liver stiffness measured on MR elastography (unit: kPa) 3) T1 relaxation time measured on T1 mapping (unit: msec) → Development of linear equation for NAFLD activity score (NAS) and Steatosis, Activity, Fibrosis (SAF) score
Fitting of observed values (NAS, SAF score) and predicted values (NAS, SAF score) → Obtaining R square (R2) (Unit: none)
Time Frame
up to 23 month
Secondary Outcome Measure Information:
Title
Fat imaging : Fat signal fraction measured on magnetic resonance(MR) spectroscopy
Description
* Fat signal fraction measured on magnetic resonance(MR) spectroscopy
high speed T2-corrected multi-echo (HISTO) MR spectroscopic technique
multiple short echo time : correction of T2 bias
long repetition time: correction of T1 bias
15 x 15 x 15-mm square-shaped region-of-interest(ROI) → Right hepatic lobe
3 times measurement → mean value was used as a representative value
unit: percentage (%)
Receiver operating characteristic (ROC) curve analysis for steatosis grade (0-3) → Obtaining cut-off values of each steatosis grade and area under the curve (AUC)
Time Frame
During scanning, up to 15 seconds
Title
Fibrosis imaging(1) : Liver stiffness measured on magnetic resonance elastography(MRE)
Description
* Magnetic resonance elastography(MRE)
60 Hz acoustic wave
Four slices were obtained for each magnetic resonance elastography(MRE) examination
Stiffness maps (elastograms) for each magnetic resonance elastography(MRE) slices were automatically generated
free-hand region-of-interest (ROI) on the right hepatic lobe
5 times measurement → mean value was used as a representative value
unit: kilopascal (kPa)
Receiver operating characteristic (ROC) curve analysis for fibrosis grade (0-4) → Obtaining cut-off values of each fibrosis grade and area under the curve (AUC)
Time Frame
During scanning, up to 20 seconds
Title
Fibrosis imaging(2) : T1 relaxation time measured on T1 mapping
Description
* T1 mapping
Shortened Modified Look Locker Inversion (shMOLLI) recovery sequence
Four slices were obtained for each T1 map
Oval-shaped region-of-interest (ROI) in the right hepatic lobe
5 times measurement → mean value was used as a representative value
unit: millisecond (msec)
Receiver operating characteristic (ROC) curve analysis for ballooning (0-2), lobular inflammation (0-3), fibrosis grade (0-4) → Obtaining cut-off values of each grade and area under the curve (AUC)
Time Frame
During scanning, up to 20 seconds
Title
Histologic interpretation(1) : Nonalcoholic fatty liver disease activity score (NAS)
Description
the sum of each histological component semiquantitatively evaluated as follows: steatosis (0-3), ballooning (0-2), and lobular inflammation (0-3)
NAS 0-2: not considered steatohepatitis
NAS 3-4: possible steatohepatitis 4/ NAS ≥5: definite steatohepatitis
Time Frame
Up to a week
Title
Histologic interpretation(1) : Steatosis, Activity, Fibrosis (SAF) score
Description
steatosis (0-3), ballooning degeneration (0-2), lobular inflammation (0-2), and fibrosis (0-4).
Nonalcoholic steatohepatitis(NASH): when steatosis is present and when both features of activity (ballooning and lobular inflammation) display at least grade 1
Unit: None
Time Frame
Up to a week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients >19 years age
Patients who had elevated aspartate transaminase(AST)/alanine transaminase(ALT) and fatty liver on abdominal ultrasonography
Patients who are clinically suspected to have nonalcoholic steatohepatitis(NASH)
Clinically suspected nonalcoholic steatohepatitis(NASH): >40 years age, metabolic syndrome, fibrosis on transient elastography(TE, Fibroscan), or elevated Fibrosis-4(FIB-4), Aspartate aminotransferase-to-platelet ratio index(APRI), nonalcoholic fatty liver disease fibrosis score(NFS) on blood tests
Patients who underwent (<6 months) or will undergo US-guided liver biopsy
Exclusion Criteria:
Chronic liver disease other than nonalcoholic fatty liver disease(NAFLD) (chronic hepatitis B or C, autoimmune hepatitis, primary biliary sclerosis)
Alcohol abuse (men, >140g/week; women, >70g/week)
Fatty liver due to medication
Contraindication to magnetic resonance imager(MRI)
Hepatocellular carcinoma
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chang Hee Lee, MD, Ph.D.
Organizational Affiliation
Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Korea University Guro Hospital
City
Seoul
State/Province
Guro-gu
ZIP/Postal Code
08308
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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Citation
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Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)
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