Accuracy of Imaging Techniques in Diagnosing Steatohepatitis and Fibrosis in NAFLD Patients

NCT04785937 | Recruiting

• 1 other identifier: 859/2018/SPER/AUSLRE
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, and when fatty liver is associated with inflammation and hepatocellular injury (steatohepatitis), it can lead to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Liver biopsy is the gold standard for NAFLD assessment but has several drawbacks. Several drugs for NASH are now in phase 2-3 trials, and if medical treatments become available, non-invasive tools to identify patients who may benefit from a therapeutic intervention will be strongly needed. Some imaging methods have shown promising potential in fibrosis and NASH diagnosis. This study aims to evaluate the diagnostic accuracy of non-invasive imaging methods, including ultrasound (US) and Magnetic Resonance (MR) techniques, in diagnosing NASH and fibrosis in patients with or at high risk of NAFLD, using liver biopsy as the reference standard. Consecutive patients with a clinical indication for liver biopsy assessment of NAFLD are enrolled in this non-inferiority study. They undergo both a liver US and a multiparametric unenhanced liver MR examination. As reference standard, histological diagnosis of fibrosis and steatohepatitis made according to the fatty liver inhibition of progression (FLIP) algorithm is used. Sensitivity and specificity of imaging parameters alone or in different combinations will be calculated with the aim of finding one or more tests with at least 90% sensitivity/specificity compared to liver biopsy.

Conditions

Non-Alcoholic Fatty Liver Disease; Steatohepatitis, Nonalcoholic; Liver Fibroses

Keywords

Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Diagnostic Ultrasound; Biopsy; Non-Inferiority Trial

Outcome Measures

Primary Outcomes (4)

• False positives

  false positives of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis

  baseline

• False negatives

  false negatives of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis

  baseline

• Sensitivity

  Sensitivity of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis

  baseline

• Specificity

  Specificity of each imaging parameter compared to liver biopsy in the diagnosis of NASH/fibrosis

  baseline

Secondary Outcomes (2)

• Correlation of quantitative imaging parameters with histopathological, demographic, anthropometric and clinical characteristics

  baseline

• Number of patients whit incomplete or unreliable imaging tests

  baseline

Study Arms (1)

Imaging and Biopsy

EXPERIMENTAL

All patients undergo both liver biopsy and liver imaging (US and MR) to assess the diagnostic performance of imaging compared to histopathological examination in the diagnosis of NASH and fibrosis.

Diagnostic Test: Ultrasound and Magnetic Resonance

Interventions

Ultrasound and Magnetic Resonance DIAGNOSTIC_TEST

liver ultrasound (US), including shear wave elastography (SWE) with liver stiffness measurement and US- fatty liver indicator (US-FLI), and a multiparametric unenhanced liver magnetic resonance examination including MR spectroscopy (MRS), Proton Density Fat Fraction (PDFF) and T2\* measurement with Multiecho technique, T1 mapping with Inversion Recovery method, and Intravoxel Incoherent Motion diffusion weighted imaging (IVIM-DWI), measuring different parameters.

Imaging and Biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical indication to perform a liver biospy for NAFLD assessment based on all of the following:
• presence of liver steatosi at ultrasound
• at least one risk factor for NASH/fibrosis (obesity, or type 2 diabetes mellitus, or metabolic syndrome)
• increased liver enzymes (at least one of: GOT\>40 U/l, GPT\>49 U/l, GGT\>75 U/l) or high NAFLD fibrosis score (\>0.675), or intermediate NAFLD fibrosis score (between -1.455 and 0.675) and increased liver stiffness at transient elastography (\>7 KPa).
• consent to participate in the study

You may not qualify if:

• age \< 18 years
• secondary causes of liver steatosis (moderate to severe alcohol consumption, steatogenic drugs)
• known diffuse liver diseases other than NAFLD (cirrhosis, viral or autoimmune hepatitis, hemochromatosis, amiloidosis, other) or previous primary or secondary liver neoplasms
• contraindications to perform liver biopsy (ascites, platelet count\<50.000/mmc, INR\>1.5, PT\>50%, serum bilirubin \>3 mg/dL)
• contraindications to perform magnetic resonance (pace-maker, claustrophobia, pregnancy, MR-unsafe metallic implants)

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead

Study Sites (1)

Azienda USL-IRCCS di Reggio Emilia

Reggio Emilia, RE, 42123, Italy

RECRUITING

Related Publications (11)

• Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018 Jan;67(1):123-133. doi: 10.1002/hep.29466. Epub 2017 Dec 1.

  PMID: 28802062 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.

  PMID: 28714183 BACKGROUND

• European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.

  PMID: 27062661 BACKGROUND

• Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014 Jan 14;20(2):475-85. doi: 10.3748/wjg.v20.i2.475.

  PMID: 24574716 BACKGROUND

• Issa D, Patel V, Sanyal AJ. Future therapy for non-alcoholic fatty liver disease. Liver Int. 2018 Feb;38 Suppl 1:56-63. doi: 10.1111/liv.13676.

  PMID: 29427492 BACKGROUND

• Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Hooker J, Sy E, Savides MT, Alquiraish MH, Valasek MA, Rizo E, Richards L, Brenner D, Sirlin CB, Loomba R. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017 Feb;152(3):598-607.e2. doi: 10.1053/j.gastro.2016.10.026. Epub 2016 Oct 27.

  PMID: 27911262 BACKGROUND

• Besutti G, Valenti L, Ligabue G, Bassi MC, Pattacini P, Guaraldi G, Giorgi Rossi P. Accuracy of imaging methods for steatohepatitis diagnosis in non-alcoholic fatty liver disease patients: A systematic review. Liver Int. 2019 Aug;39(8):1521-1534. doi: 10.1111/liv.14118. Epub 2019 May 8.

  PMID: 30972903 BACKGROUND

• Ballestri S, Lonardo A, Romagnoli D, Carulli L, Losi L, Day CP, Loria P. Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver Int. 2012 Sep;32(8):1242-52. doi: 10.1111/j.1478-3231.2012.02804.x. Epub 2012 Apr 22.

  PMID: 22520641 BACKGROUND

• Eddowes PJ, McDonald N, Davies N, Semple SIK, Kendall TJ, Hodson J, Newsome PN, Flintham RB, Wesolowski R, Blake L, Duarte RV, Kelly CJ, Herlihy AH, Kelly MD, Olliff SP, Hubscher SG, Fallowfield JA, Hirschfield GM. Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2018 Mar;47(5):631-644. doi: 10.1111/apt.14469. Epub 2017 Dec 22.

  PMID: 29271504 BACKGROUND

• Pavlides M, Banerjee R, Tunnicliffe EM, Kelly C, Collier J, Wang LM, Fleming KA, Cobbold JF, Robson MD, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017 Jul;37(7):1065-1073. doi: 10.1111/liv.13284. Epub 2017 May 30.

  PMID: 27778429 BACKGROUND

• Bedossa P; FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology. 2014 Aug;60(2):565-75. doi: 10.1002/hep.27173. Epub 2014 Jun 26.

  PMID: 24753132 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Interventions

Ultrasonography; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography

Study Officials

• Pierpaolo Pattacini, MD

  Azienda USL - IRCCS di Reggio Emilia

  STUDY DIRECTOR

Central Study Contacts

Giulia Besutti, MD

CONTACT

+390522296369; giulia.besutti@ausl.re.it

Pierpaolo Pattacini, MD

CONTACT

+390522296369; pierpaolo.pattacini@ausl.re.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2021
• First Posted: March 8, 2021
• Study Start: January 1, 2019
• Primary Completion: June 1, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)