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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03375008
Other study ID # KUGH16184
Secondary ID
Status Completed
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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