Screening in Primary Care of Advanced Liver Fibrosis in NAFLD And/or Alcoholic Patients (SOPRANO)

The primary objective of the SOPRANO study is to compare two blood fibrosis tests, the eLIFT and the FibroMeter, for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers.

Study Overview

• Status: Recruiting
• Conditions: Liver Fibrosis; Non-alcoholic Fatty Liver Disease (NAFLD); Alcoholic Liver Disease (ALD)
• Intervention / Treatment: Diagnostic test: eLIFT

Detailed Description

Chronic liver diseases (CLD) are responsible for 17 000 deaths each year in France (cirrhosis: 8 000, liver cancer: 9 000). Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the two main causes of CLD in France, affecting respectively 25% and 12% of the adult general population. A subset of these patients develops advanced liver fibrosis (ALF), which requires referral to the specialist for specific evaluation and management to avoid the occurrence of cirrhosis and its life-threatening complications. General practitioners (GPs) are the first-line physicians in front of the large population of NAFLD and/or ALD patients. It is very difficult for GPs to identify the patients who develop ALF and require referral to the specialist, as their physical examination, usual biology and ultrasonography remain normal.

The non-invasive diagnosis of liver fibrosis is now available with elastography devices and blood tests. Elastography is a very accurate method but it is available only in few specialised centers. Specialised blood tests are available to all physicians, but they are quite expensive and not reimbursed with therefore limited use in clinical practice. Consequently, liver fibrosis remains unevaluated in most patients with NAFLD and/or ALD, which explains why a lot are too late diagnosed at the stage of cirrhosis complications with poor short-term survival.

The eLIFT isa new blood fibrosis test specifically dedicated for GPs with simple parameters and easy "by head" calculation. The simple eLIFT was compared with the specialised blood test FibroMeter for the diagnosis of ALF in an cohort of 1024 biopsy-proven NAFLD and/or ALD patients. eLIFT was little less accurate than FibroMeter (AUROC: 0.78 vs 0.81). Using the recommended cut-offs (eLIFT ≥8, FibroMeter ≥0.46), eLIFT was more sensitive than FibroMeter (86% vs 77%), whereas FibroMeter was highly more specific (71% vs 51%). These results position eLIFT and FibroMeter as interesting tools for the screening of ALF in large populations.

As the preliminary results come from very selected patients, i.e. patients from tertiary centers who underwent a liver biopsy, it's necessary nox to evaluate in the real condition of primary care setting whether the use of eLIFT or FibroMeter will help GPs to screen ALF in their asymptomatic NAFLD and ALD patients.

• Study Type: Interventional
• Enrollment (Estimated): 1788
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: William BELLANGER, PH; Phone Number: +33 02 41 73 58 10; Email: william.bellanger@univ-angers.fr
• Study Contact Backup: Name: Marc De Saint Loup; Phone Number: +33 0241357812; Email: madesaintloup@chu-angers.fr

Study Locations

• France
  • Angers, France, 49000
    • Active, not recruiting
    • CHU Angers
  • Angers, France, 49000
    • Recruiting
    • ANGERS
    • Contact: David FORTIER, MD
  • Bécon-les-Granits, France, 49370
    • Completed
    • BECON
  • Chalonnes-sur-Loire, France, 49290
    • Completed
    • Chalonnes
  • Combourg, France, 35270
    • Completed
    • COMBOURG
  • Liffré, France, 35340
    • Completed
    • LIFFRE
  • Montreuil-Bellay, France, 49260
    • Completed
    • Montreuil
  • Rennes, France, 35000
    • Not yet recruiting
    • RENNES - Armagnac, Churchill
    • Contact: Lise SEIGNEURET, MD
  • Rennes, France, 35033
    • Active, not recruiting
    • Chu Rennes
  • Rennes, France, 35000
    • Completed
    • RENNES - Kennedy
  • Segré, France, 49500
    • Completed
    • SEGRE
  • Val-Couesnon, France, 35560
    • Recruiting
    • Val Couesnon
    • Contact: Enora CORNU, MD; Phone Number: +33 02 99 98 31 44; Email: enoracornu@yahoo.fr
    • Contact: Benjamin BASTIAN - princial investigator of Tremblay, MD
    • Contact: Enora CORNU - principal investigator of Antrain, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• NAFLD and/or ALD patient defined by at least 1 of the following criteria:

  • Excessive alcohol consumption: higher than 210 g / week (men), or 140 g / week (women)
  • Type 2 diabetes
  • at least 2 metabolic factors among BMI higher than or equal to 25 kg / m 2; Elevated blood pressure (antihypertensive drug, or systolic blood pressure higher than or equal to 130mmHg, or diastolic blood pressure higher than or equal to 85mmHg), Dyslipidemia (lipid-lowering drug, or HDL cholesterol lower to 40mg/dl (men) / 50mg/dl (women), or triglycerides higher than or equal to150mg/dl); Hyperferritinemia (higher than upper limit of normal from the laboratory)
  • Bright liver at ultrasonography without steatosis-inducing drug(systemic corticosteroids, tamoxifen, amiodarone, methotrexate)

Following a protocol amendment, the 3 last investigating primary care centres will include NAFLD and/or ALD patients according to these updated criteria:

• Excessive alcohol consumption: >210 g/week in men or >140 g/week in women,
• AND/OR type 2 diabetes treated with insulin and/or at least two other anti-diabetic treatments,

• AND with the following stratification:

  40% with excessive alcohol consumption 40% with type 2 diabetes treated with insulin and/or at least two other anti-diabetic treatments 20% with both conditions (excessive alcohol consumption, AND type 2 diabetes treated with insulin and/or at least two other anti-diabetic treatments)

• Patient's agreement to have a blood sample collected in a local laboratory participating in the study
• Subjects covered by or having the rights to medical care assurance
• Written informed consent obtained from subject

Exclusion Criteria:

• Already ongoing specialized follow-up for a chronic liver disease
• Altered health status with poor short-term prognosis, not compatible with a screening procedure
• Decompensated cirrhosis (hepatic encephalopathy, jaundice, ascites, variceal bleeding, hepatorenal syndrome)
• Acute infection
• Pregnancy, breastfeeding
• Persons in detention by judicial or administrative decision
• Person admitted to a health or social establishment for purposes other than research
• Person subject to a legal protection measure
• Person unable to express consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• 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: Diagnostic Test: e-LIFT; only one arm because diagnostic study evaluating blood test using elastometry and liver biopsy as reference	Diagnostic test: eLIFT; Diagnostic procedure: elastography devices, blood tests (e-LIFT + Fibrometer), liver biopsy if necessary (elastometry ≥ 8 kPa and < 15 kPa)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the eLIFT test for advanced liver fibrosis	Rate of patients with advanced liver fibrosis correctly identified by the eLIFT test	1 day
Sensitivity of the Fibrometer test for advanced liver fibrosis	Rate of patients with advanced liver fibrosis correctly identified by the Fibrometer test	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of patients referred to the specialist following the screening procedure, with eLIFT test	Rate of patients with positive screening test (eLIFT ≥8)	1 day
rate of patients referred to the specialist following the screening procedure, with FibroMeter test	Rate of patients with positive screening test (FibroMeter ≥0.46)	1 day
Rate of "unnecessary referrals" to the specialist with eLIFT test	Rate of patients with positive screening test (eLIFT ≥8) but without final diagnosis of ALF	1 month
Rate of "unnecessary referrals" to the specialist with Fibrometer test	Rate of patients with positive screening test (FibroMeter ≥0.46) but without final diagnosis of ALF	1 month
Number of hepatocellular carcinoma adetected following the screening procedure, with comparison between eLIFT and FibroMeter strategies	Number of patients with hepatocellular carcinoma (diagnosed on MRI by the recommended radiological criteria: hyperenhancement on the arterial phase and washout on the portal venous phase, or by liver biopsy);	1 month
Number of gastroesophageal varices at risk of bleeding detected following the screening procedure, with comparison between eLIFT and FibroMeter strategies	Number of patients with gastroesophageal varices at risk of bleeding (diagnosed by upper-gastrointestinal endoscopy: medium-large varices or small varices with red wall marks)	1 month
directs costs by type of disease such as ALF, hepatocellular carcinoma, gastroesophageal varices at risk of bleeding with comparison between eLIFT and FibroMeter strategies	Mean direct cost per patient; mean direct cost generated to detect one patient with ALF, one patient with hepatocellular carcinoma, one patient with gastroesophageal varices at risk of bleeding	1 month
eLIFT and FibroMeter screening procedures as a function of the cause of the underlying liver disease (NAFLD, ALD, or mixed NAFLD+ALD)	Rate of patient with ALF, positive screening test, hepatocellular carcinoma, gastroesophageal varices at risk of bleeding, and mean cost, with comparison between NAFLD, ALD, and mixed NAFLD+ALD subgroups	1 month
the accuracy of a sequential strategy using eLIFT as first-line test and FibroMeter as second-line test	Rate of patients with ALF diagnosed by a stepwise algorithm using eLIFT ≥8 then, if positive, FibroMeter ≥0.46	1 day
patient adherence to the screening of advanced liver fibrosis	Rate of patients included in the study who did not achieve the required screening procedures	1 month
most relevant risk factor of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care	Risk factors among clinical characteristics, alcohol consumption, metabolic parameters independently associated with ALF diagnosis	1 day
specialized blood test ELF for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers	Same endpoints than primary and secondaries 1 to 11, but using the recommended 9.8 threshold for ELF	1 day
Camden and Islington pathway (FIB4 then ELF) for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers,	Same endpoints than primary and secondaries 1 to 11, but using using the Camden and Islington pathway	1 day
Camden and Islington pathway , with comparison of sequential strategy eLIFT then FibroMeter	Same endpoints than primary and secondaries 1 to 11, but using using the Camden and Islington pathway	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): December 13, 2025
• Study Completion (Estimated): March 13, 2026

Study Registration Dates

• First Submitted: December 28, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcohol-Induced Disorders; Fibrosis; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Liver Diseases, Alcoholic
• Other Study ID Numbers: 2022-A02148-35

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
• product manufactured in and exported from the U.S.: No