Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)

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

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)

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).

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)

* 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)

* 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)

* 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)

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

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

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

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