Non-invasive Evaluation of Liver Fibrosis, Steatosis, and NASH in NAFLD

Non-invasive Evaluation of Liver Fibrosis, Steatosis, and Nonalcoholic Steatohepatitis in Biopsy-Proven NAFLD Patients

1. To evaluate hepatic fibrosis and steatosis using MR imaging, transient elastography (TE), and serum biomarker
2. To develop non-invasive diagnosis marker for NASH and advanced fibrosis

Study Overview

• Status: Unknown
• Conditions: Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver
• Intervention / Treatment: Diagnostic test: Imaging and serologic evaluation of fibrosis and steatosis

Detailed Description

As nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease, non-invasive diagnosis of disease severity in NAFLD is urgently needed. In this study, the investigators compared hepatic fibrosis and steatosis using MR imaging and transient elastography (TE) and tried to find non-invasive diagnostic marker for NASH and advanced fibrosis.

This is a multicenter prospective study of patients with biopsy-proven NAFLD. The patients were underwent laboratory test, liver biopsy, MRI and TE within 6 months of enrollment. MRI examination included MR spectroscopy (MRS), and MR elastography (MRE). TE measured liver stiffness and controlled attenuation parameter (CAP).

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Seung-hoe Song, MBE; Phone Number: 82-2-2626-1635; Email: ssessong@korea.ac.kr
    • Contact: Ji-young Lee; Phone Number: 82-2-2626-2279; Email: ljy@kumc.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients >19 years age
• Patients who had elevated aspartate transaminase(AST)/alanine transaminase(ALT) or fatty liver on abdominal ultrasonography
• Patients who are clinically suspected to have nonalcoholic steatohepatitis(NASH): >40 years age, BMI >25, multiple features of the metabolic syndrome, presence of diabetes mellitus (DM) , fibroscan > 6 kilopascal (kPa), platelet count < 150,000 /ml, and other patients suspected to progress clinically or requiring diagnosis
• 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 cholangitis)
• Excessive alcohol consumption (weekly men >140g and women >70g)
• Fatty liver due to medication
• Decompensated liver cirrhosis
• Contraindication to magnetic resonance imager(MRI)
• Malignancy or other systemic disease
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biopsy proven NAFLD patients; 150 subjects who are diagnosed with NAFLD with biopsy from September 2016 to October 2018.	Diagnostic test: Imaging and serologic evaluation of fibrosis and steatosis; Imaging evaluation: Fibroscan, MRI scan for evaluation of fibrosis and steatosis in biopsy proven NAFLD patients Serologic evaluation: serologic test for evaluation of fibrosis and steatosis in biopsy proven NAFLD patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of scoring system for diagnosis of NASH	Development of scoring system for diagnosis of NASH using cox regression analysis	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of hepatic fibrosis using fibroscan	Assessment of hepatic fibrosis using fibroscan with transient elastography (kilopascals) (kPa)	up to 24 months
Evaluation of hepatic steatosis using fibroscan	Assessment of hepatic steatosis using fibroscan with CAP (Controlled Attenuation Parameter) (dB/m)	up to 24 months
Evaluation of hepatic fibrosis using MRI	Assessment of hepatic fibrosis using MRI with MR elastography (MRE) (kPa)	up to 24 months
Evaluation of hepatic steatosis using MRS	Assessment of hepatic steatosis using fibroscan with MR spectrography (MRS) (%)	up to 24 months
Evaluation of hepatic fibrosis using serologic marker	Assessment of hepatic fibrosis using AST to Platelet Ratio Index (APRI)	up to 24 months

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Investigators: Principal Investigator: Jong Eun Yeon, MD, Ph.D., Prefessor

Publications and helpful links

General Publications

• 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. doi: 10.1002/hep.20701.
• 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. No abstract available.
• 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.
• 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.
• 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.
• 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. doi: 10.1016/0168-8278(95)80226-6. No abstract available.
• 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. doi: 10.1111/j.1572-0241.1999.01377.x.
• SCHEUER PJ, WILLIAMS R, MUIR AR. Hepatic pathology in relatives of patients with haemochromatosis. J Pathol Bacteriol. 1962 Jul;84:53-64. No abstract available.
• 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(1):69. doi: 10.1186/1532-429X-12-69.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): August 31, 2019
• Study Completion (Anticipated): August 31, 2019

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: October 29, 2018
• First Posted (Actual): October 31, 2018

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Biomarker; Magnetic resonance imager(MRI); Nonalcoholic fatty liver disease(NAFLD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2016GR0302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No