Comparison of Two sTRAtegies For the Non-Invasive Diagnosis of advanCed Liver Fibrosis in NAFLD (TRAFIC)

NAFLD, closely linked to overweight and insulin resistance, has reached 25% prevalence worldwide. Advanced liver fibrosis(ALF) must be accurately diagnosed in NAFLD because it defines a subgroup of patients with impaired prognosis, and these patients need a specific management to prevent the occurrence of liver-related complication. Relatively few NAFLD patients develop ALF and it is a challenge for physicians to identify them.

Liver biopsy is the reference for liver fibrosis evaluation but this invasive procedure cannot be first-line used in NAFLD. Non-invasive diagnosis of liver fibrosis is now available, especially liver stiffness measurement (LSM) with Fibroscan and blood fibrosis tests. However, Fibroscan is a costly device available only in few specialized centres with thus poor accessibility in face of the large NAFLD population. Blood fibrosis tests can be performed by every physician and are distinguished as "complex" or "simple". Because they include specialized biomarkers, complex blood fibrosis tests are accurate for the diagnosis of ALF but they are quite expensive and not reimbursed, with therefore limited use in clinical practice. Simple blood fibrosis tests have the advantage to include cheap and easy-to-obtain biomarkers with simple calculation thanks to free websites or smartphone applications. Simple blood fibrosis tests are globally less accurate than complex blood fibrosis tests or Fibroscan but, used with a high-sensitivity cut-off, they have the high interest of being able to accurately rule out advanced fibrosis in a significant proportion of NAFLD patients.

Recently, two sequential diagnostic procedures have been developed for the diagnosis of ALF with the idea to combine the advantages of the different kind of fibrosis tests: the FIB4-Fibroscan (FIB4-FS) and the eLIFT-FibroMeterVCTE (eLIFT-FMVCTE) algorithms. These algorithms include as first-line procedure a simple blood fibrosis test (FIB4 or eLIFT) which identifies the patients who require a further second-line evaluation with a more accurate non-invasive test (Fibroscan or FibroMeterVCTE). Liver biopsy is finally used as third-line procedure in patients for whom the diagnosis remains undetermined. Such algorithms have the advantage to limit the use of complex fibrosis tests only to a subset of at risk-patients.

The TRAFIC study compare two strategies for the diagnosis of ALF in NAFLD patients: the FIB4-Fibroscan algorithm and the eLIFT-FibroMeterVCTE algorithm

Study Overview

• Status: Recruiting
• Conditions: NAFLD
• Intervention / Treatment: Diagnostic test: blood tests

Detailed Description

FIB4-FS and the eLIFT-FMVCTE were previosuly directly compared in a database of biopsy-proven NAFLD patients. These two algorithms showed a very good >80% diagnostic accuracy for advanced fibrosis and a very low <15% rate of liver biopsy requirement. The eLIFT-FMVCTE had a significantly higher diagnostic accuracy (84.6% vs 80.6%, p=0.15), was more specific, and provided higher negative and positive predictive value and higher non-invasive diagnostic accuracy. Finally, these preliminary results suggested the eLIFT-FMVCTE was most suitable for clinical practice than the FIB4-FS. However, because almost all these patients from this preliminary comparative study came from the population where the eLIFT-FMVCTE was developed with thus an optimism bias, the results from this direct comparison require further validation.

Therefore, FIB4-FS and the eLIFT-FMVCTE algorithms must now be evaluated and compared in an independent population of NAFLD patients to determine which strategy is the best one for clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 1045
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marc de Saint Loup; Phone Number: +33241357812; Email: madesaintloup@chu-angers.fr
• Study Contact Backup: Name: Jérôme Boursier, MD-PHD; Phone Number: +33241353410; Email: jeboursier@chu-angers.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • University hospital of Angers
    • Contact: Jerome Boursier
  • Besançon, France
    • Not yet recruiting
    • University Hospital of Besancon
    • Contact: Tierry Thevenot; Phone Number: +333 81 66 84 21; Email: tthevenot@chu-besancon.fr
  • Bobigny, France
    • Not yet recruiting
    • Avicenne Hospital (Greater Paris University Hospitals)
    • Contact: Pierre Nahon
  • Dijon, France
    • Recruiting
    • University Hospital of Dijon
    • Contact: Marianne Latournerie
  • La Roche-sur-Yon, France
    • Recruiting
    • Departemental Hospital Center of Vendée
    • Contact: Matthieu Schnee
  • La Tronche, France
    • Active, not recruiting
    • University hospital of Grenoble
  • Lille, France
    • Active, not recruiting
    • University Hospital of Lille
  • Limoges, France
    • Active, not recruiting
    • University Hospital of Limoges
  • Lyon, France
    • Recruiting
    • La Croix Rousse Hospital
    • Contact: Maximo Levrero
  • Lyon, France
    • Not yet recruiting
    • Edouard Herriot Hospital
    • Contact: Jérôme Dumortier; Phone Number: +334 72 11 01 46; Email: jerome.dumortier@chu-lyon.fr
  • Marseille, France
    • Not yet recruiting
    • Saint Joseph Hospital
    • Contact: Marc Bourliere; Phone Number: +334 91 80 82 35; Email: mbourliere@hopital-saint-joseph.fr
  • Montpellier, France
    • Recruiting
    • University Hospital of Montpellier
    • Contact: Stéphanie Faure
  • Nantes, France
    • Active, not recruiting
    • University Hospital of Nantes
  • Paris, France
    • Not yet recruiting
    • Cochin Hospital
    • Contact: Lucia Parlati; Phone Number: +331 58 41 29 88; Email: lucia.parlati@aphp.fr
  • Paris, France
    • Not yet recruiting
    • La Pitié Salpétrière Hospital (Greater Paris University Hospitals)
    • Contact: Vlad Ratziu
  • Paris, France
    • Active, not recruiting
    • Saint-Antoine Hospital (Greater Paris University Hospitals)
  • Pessac, France
    • Active, not recruiting
    • University Hospital of Bordeaux
  • Rennes, France
    • Active, not recruiting
    • University Hospital of Rennes
  • Tours, France
    • Active, not recruiting
    • University hospital of Tours
  • Vandœuvre-lès-Nancy, France
    • Not yet recruiting
    • University Hospital of Nancy
    • Contact: Jean-Pierre Bronowicki; Phone Number: +333 83 15 33 54; Email: jp.bronoiwicki@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Presence of NAFLD as defined by :

   • The presence of liver steatosis as assessed by ultrasonography (bright liver) or magnetic resonance imaging/spectroscopy (fat fraction >5.6%) or Controlled Attenuation Parameter (≥248 dB/m)
   • The absence of steatosis-inducing drugs (systemic corticosteroids, methotrexate, amiodarone, tamoxifen)
   • The absence of excessive alcohol consumption (<210 g/week in men or <140 g/week in women)
   • The absence of other causes of chronic liver disease (chronic viral hepatitis B or C, hemochromatosis, auto-immune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease alpha-1-antitrypsin deficiency).
2. Age ≥18 years and ≤80 years
3. Affiliated person or beneficiary of a social security regime
4. Written informed consent of the patient who agree to comply with the study protocol.

Exclusion Criteria:

1. Decompensated cirrhosis (ascites, variceal bleeding, hepatic encephalopathy, liver failure, hepato-renal syndrome)
2. Hepatocellular carcinoma
3. Inability to safely undergo liver biopsy
4. Participation in other intervention study with drug protocol treatment in progress at the time of inclusion or within one month prior to inclusion in the study.
5. Pregnant, breastfeeding or parturient woman
6. Person restricted by judicial or administrative decision
7. Person under psychiatric care under restraint
8. Person subject to a legal protection measure
9. Person unable to express consent

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

Other: Single ARM; Only one arm

Diagnostic test: blood tests; Single arm : all NAFLD patients evaluating the FIB4-FS and the eLIFT-FMVCTE with two patient groups considered at inclusion: Low-risk group (neither metabolic syndrome nor AST ≥35 UI/l): Liver biopsy won't be mandatory in this group because of the very low risk of advanced fibrosis (4%). These patients will be considered as having no-mild F0-2 liver fibrosis and the study visit will be scheduled for clinical data recording, blood sampling, and LSM with Fibroscan. Liver biopsy could still be performed in the low-risk group if the investigator deems it is required for the clinical management of the patient. At-risk group (presence of a metabolic syndrome and/or AST ≥35 UI/l): Because of the increased prevalence of significant liver lesions in this group, the patients will have a liver biopsy with clinical data recording, blood sampling, and Fibroscan the same day.; Other Names: elastography; liver biopsy if required; biobank

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients correctly classified for advanced liver fibrosis	Rate of patients correctly classified for advanced liver fibrosis, with comparison between the FIB4-FS and eLIFT-FMVCTE algorithms	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity for advanced fibrosis	Sensitivity for advanced fibrosis, with comparison between the FIB4-FS and eLIFT-FMVCTE algorithms	2 months
Parameters influencing the diagnostic accuracy of FIB4-FS and eLIFT-FMVCTE algorithms	Parameters independently associated by multivariate analysis with the rate of patients correctly classified for advanced liver fibrosis	2 months
Rate of patients correctly classified for advanced liver fibrosis as a function of the prevalence of advanced fibrosis	Rate of patients correctly classified for advanced liver fibrosis in samples generated by resampling methods with different prevalence of advanced fibrosis (5%, 10%, 15%, 20% and 25%), with comparison between FIB4-FS and eLIFT-FMVCTE algorithms	2 months
Effect of the choice of the Fibroscan probe on the diagnostic accuracy of FIB4-FS and eLIFT-FMVCTE algorithms	Rate of patients correctly classified for advanced fibrosis by the algorithms calculated with either LSMAUTO results (i.e., LSM results obtained with the probe, M or XL, which is automatically detected and recommended by the Fibroscan device), or only LSMM results (i.e., LSM results obtained with the M probe), or only LSMXL results (i.e., LSM results obtained with the XL probe).	2 months
To validate new biomarkers in a large independent NAFLD population	AUROC for advanced fibrosis, with comparison between the new biomarkers and existing fibrosis tests	2 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Estimated): October 7, 2028
• Study Completion (Estimated): December 7, 2028

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: NAFLD; diagnosis; AdvanCed Liver Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fatty Liver; Pathological Conditions, Signs and Symptoms; Disease; Non-alcoholic Fatty Liver Disease; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Ultrasonography; Hematologic Tests; Elasticity Imaging Techniques
• Other Study ID Numbers: 2020-A01920-39

Drug and device information, study documents

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