Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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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
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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).

Official Title
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Development of Non-invasive Magnetic Resonance Imaging Diagnostic Method for Nonalcoholic Steatohepatitis(NASH)

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Diagnostic Test: Imaging diagnostic and biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imaging diagnostic and biopsy<br>47 subjects who are suspected NASH from June 2016 to December 2017. | Diagnostic Test: Imaging diagnostic and biopsy<br>* Liver biopsy and MRI scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | up to 23 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | During scanning, up to 15 seconds | 
| 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) | During scanning, up to 20 seconds | 
| 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) | During scanning, up to 20 seconds | 
| 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 | Up to a week | 
| 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 | Up to a week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging diagnostic, Magnetic resonance imager(MRI), Nonalcoholic fatty liver disease(NAFLD)