Clinical trial NCT05699018: Screening in Primary Care of Advanced Liver Fibrosis in NAFLD And/or Alcoholic Patients
Official title: Screening in Primary Care of Advanced Liver Fibrosis in NAFLD And/or Alcoholic Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)
Alcoholic Liver Disease (ALD)
Liver Fibrosis
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2023-01-26
Enrollment: 1788
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The SOPRANO study is a multicenter prospective comparative diagnostic study . Evaluation of a simple blood test (e-LIFT) for the diagnosis of advanced liver fibrosis.

Reference for advanced liver diagnosis : composite criteria :

* Elastometry between 8 kPa and 14.9 kPa and histologic evaluation of fibrosis ≥ F3 (NASH CRN ) OR
* Elastometry ≥ 15 kPa
Primary purpose: SCREENING

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity of the eLIFT test for advanced liver fibrosis
timeFrame: 1 day
measure: Sensitivity of the Fibrometer test for advanced liver fibrosis
timeFrame: 1 day
Secondary outcomes:
measure: rate of patients referred to the specialist following the screening procedure, with eLIFT test
timeFrame: 1 day
measure: rate of patients referred to the specialist following the screening procedure, with FibroMeter test
timeFrame: 1 day
measure: Rate of "unnecessary referrals" to the specialist with eLIFT test
timeFrame: 1 month
measure: Rate of "unnecessary referrals" to the specialist with Fibrometer test
timeFrame: 1 month
measure: Number of hepatocellular carcinoma adetected following the screening procedure, with comparison between eLIFT and FibroMeter strategies
timeFrame: 1 month
measure: Number of gastroesophageal varices at risk of bleeding detected following the screening procedure, with comparison between eLIFT and FibroMeter strategies
timeFrame: 1 month
measure: directs costs by type of disease such as ALF, hepatocellular carcinoma, gastroesophageal varices at risk of bleeding with comparison between eLIFT and FibroMeter strategies
timeFrame: 1 month
measure: eLIFT and FibroMeter screening procedures as a function of the cause of the underlying liver disease (NAFLD, ALD, or mixed NAFLD+ALD)
timeFrame: 1 month
measure: the accuracy of a sequential strategy using eLIFT as first-line test and FibroMeter as second-line test
timeFrame: 1 day
measure: patient adherence to the screening of advanced liver fibrosis
timeFrame: 1 month
measure: most relevant risk factor of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care
timeFrame: 1 day
measure: specialized blood test ELF for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers
timeFrame: 1 day
measure: 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,
timeFrame: 1 day
measure: Camden and Islington pathway , with comparison of sequential strategy eLIFT then FibroMeter
timeFrame: 1 day
Other outcomes:
Locations:
city: Angers
country: France
facility: ANGERS
city: Angers
country: France
facility: CHU Angers
city: Bécon-les-Granits
country: France
facility: BECON
city: Chalonnes-sur-Loire
country: France
facility: Chalonnes
city: Combourg
country: France
facility: COMBOURG
city: Liffré
country: France
facility: LIFFRE
city: Montreuil-Bellay
country: France
facility: Montreuil
city: Rennes
country: France
facility: RENNES - Armagnac, Churchill
city: Rennes
country: France
facility: RENNES - Kennedy
city: Rennes
country: France
facility: CHU Rennes
city: Segré
country: France
facility: SEGRE
city: Val-Couesnon
country: France
facility: Val Couesnon
Study officials:
References: