Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03375008
• Other study ID #: KUGH16184
• Status: Completed
• Phase: N/A
• Start date: September 8, 2016
• Est. completion date: August 7, 2018

Study information

• Verified date: May 2019
• Source: Korea University Guro Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. To evaluate feasibility of using multiparametric Magnetic resonance(MR) imaging to predict nonalcoholic steatohepatitis(NASH)

2. To develop non-invasive diagnosis tool using multiparametric Magnetic resonance(MR) imaging for nonalcoholic steatohepatitis(NASH)

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: August 7, 2018
• Est. primary completion date: August 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Patients >19 years age

2. Patients who had elevated aspartate transaminase(AST)/alanine transaminase(ALT) and fatty liver on abdominal ultrasonography

3. 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

4. Patients who underwent (<6 months) or will undergo US-guided liver biopsy

Exclusion Criteria:

1. Chronic liver disease other than nonalcoholic fatty liver disease(NAFLD) (chronic hepatitis B or C, autoimmune hepatitis, primary biliary sclerosis)

2. Alcohol abuse (men, >140g/week; women, >70g/week)

3. Fatty liver due to medication

4. Contraindication to magnetic resonance imager(MRI)

5. Hepatocellular carcinoma

6. Pregnancy

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Diagnostic Test:
• Imaging diagnostic and biopsy
Liver biopsy and MRI scan

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital	Seoul	Guro-gu

Sponsors (1)

Lead Sponsor	Collaborator
Korea University Guro Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12. — View Citation

Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74. — View Citation

Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. — View Citation

Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995 Jun;22(6):696-9. Review. — View Citation

Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. — View Citation

Park YS, Lee CH, Kim JH, Kim BH, Kim JH, Kim KA, Park CM. Effect of Gd-EOB-DTPA on hepatic fat quantification using high-speed T2-corrected multi-echo acquisition in (1)H MR spectroscopy. Magn Reson Imaging. 2014 Sep;32(7):886-90. doi: 10.1016/j.mri.2014.04.010. Epub 2014 Apr 24. — View Citation

Piechnik SK, Ferreira VM, Dall'Armellina E, Cochlin LE, Greiser A, Neubauer S, Robson MD. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold. J Cardiovasc Magn Reson. 2010 Nov 19;12:69. doi: 10.1186/1532-429X-12-69. — View Citation

Poynard T, Lenaour G, Vaillant JC, Capron F, Munteanu M, Eyraud D, Ngo Y, M'Kada H, Ratziu V, Hannoun L, Charlotte F. Liver biopsy analysis has a low level of performance for diagnosis of intermediate stages of fibrosis. Clin Gastroenterol Hepatol. 2012 Jun;10(6):657-63.e7. doi: 10.1016/j.cgh.2012.01.023. Epub 2012 Feb 14. — View Citation

SCHEUER PJ, WILLIAMS R, MUIR AR. Hepatic pathology in relatives of patients with haemochromatosis. J Pathol Bacteriol. 1962 Jul;84:53-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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