Screening in Primary Care of Advanced Liver Fibrosis in NAFLD and/or Alcoholic Patients

Liver Fibrosis Clinical Trial

— SOPRANO  

Official title:

Screening in Primary Care of Advanced Liver Fibrosis in NAFLD and/or Alcoholic Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05699018
• Other study ID #: 2022-A02148-35
• Status: Recruiting
• Phase: N/A
• Start date: March 13, 2023
• Est. completion date: December 15, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Angers
• Contact: William BELLANGER, PH
• Phone: 02 41 73 58 10
• Email: william.bellanger[@]univ-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1788
• Est. completion date: December 15, 2025
• Est. primary completion date: May 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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)

• 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

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Liver Diseases
• Liver Diseases, Alcoholic
• Liver Fibrosis
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease (NAFLD)

Intervention

Diagnostic Test:
• eLIFT
Diagnostic procedure: elastography devices, blood tests (e-LIFT + Fibrometer), liver biopsy if necessary (elastometry = 8 kPa and < 15 kPa)

Locations

Country	Name	City	State
France	ANGERS	Angers
France	CHU Angers	Angers
France	BECON	Bécon-les-Granits
France	Chalonnes	Chalonnes-sur-Loire
France	COMBOURG	Combourg
France	LIFFRE	Liffré
France	Montreuil	Montreuil-Bellay
France	CHU Rennes	Rennes
France	RENNES - Armagnac, Churchill	Rennes
France	RENNES - Kennedy	Rennes
France	SEGRE	Segré
France	Val Couesnon	Val-Couesnon

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of the eLIFT test for advanced liver fibrosis	Rate of patients with advanced liver fibrosis correctly identified by the eLIFT test	1 day
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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