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

Sponsor

University Hospital, Angers (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05699018

Collaborator

(none)

1,788

Enrollment

Locations

Arm

18.8

Anticipated Duration (Months)

298

Patients Per Site

15.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Fatty Liver Disease (NAFLD) Alcoholic Liver Disease (ALD) Liver Fibrosis	Diagnostic Test: eLIFT	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1788 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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 kPaThe 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

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

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

Anticipated Study Start Date :

Feb 20, 2023

Anticipated Primary Completion Date :

Sep 15, 2024

Anticipated Study Completion Date :

Sep 15, 2024

Arms and Interventions

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 (elstometry ≥ 8 kPa and < 15 kPa)

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 (elstometry ≥ 8 kPa and < 15 kPa)

Outcome Measures

Primary Outcome Measures

Sensitivity of the eLIFT test for advanced liver fibrosis [1 day]
Rate of patients with advanced liver fibrosis correctly identified by the eLIFT test
Sensitivity of the Fibrometer test for advanced liver fibrosis [1 day]
Rate of patients with advanced liver fibrosis correctly identified by the Fibrometer test

Secondary Outcome Measures

rate of patients referred to the specialist following the screening procedure, with eLIFT test [1 day]
Rate of patients with positive screening test (eLIFT ≥8)
rate of patients referred to the specialist following the screening procedure, with FibroMeter test [1 day]
Rate of patients with positive screening test (FibroMeter ≥0.46)
Rate of "unnecessary referrals" to the specialist with eLIFT test [1 month]
Rate of patients with positive screening test (eLIFT ≥8) but without final diagnosis of ALF
Rate of "unnecessary referrals" to the specialist with Fibrometer test [1 month]
Rate of patients with positive screening test (FibroMeter ≥0.46) but without final diagnosis of ALF
Number of hepatocellular carcinoma adetected following the screening procedure, with comparison between eLIFT and FibroMeter strategies [1 month]
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);
Number of gastroesophageal varices at risk of bleeding detected following the screening procedure, with comparison between eLIFT and FibroMeter strategies [1 month]
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)
directs costs by type of disease such as ALF, hepatocellular carcinoma, gastroesophageal varices at risk of bleeding with comparison between eLIFT and FibroMeter strategies [1 month]
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
eLIFT and FibroMeter screening procedures as a function of the cause of the underlying liver disease (NAFLD, ALD, or mixed NAFLD+ALD) [1 month]
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
the accuracy of a sequential strategy using eLIFT as first-line test and FibroMeter as second-line test [1 day]
Rate of patients with ALF diagnosed by a stepwise algorithm using eLIFT ≥8 then, if positive, FibroMeter ≥0.46
patient adherence to the screening of advanced liver fibrosis [1 month]
Rate of patients included in the study who did not achieve the required screening procedures
most relevant risk factor of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care [1 day]
Risk factors among clinical characteristics, alcohol consumption, metabolic parameters independently associated with ALF diagnosis
specialized blood test ELF for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers [1 day]
Same endpoints than primary and secondaries 1 to 11, but using the recommended 9.8 threshold for ELF
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, [1 day]
Same endpoints than primary and secondaries 1 to 11, but using using the Camden and Islington pathway
Camden and Islington pathway , with comparison of sequential strategy eLIFT then FibroMeter [1 day]
Same endpoints than primary and secondaries 1 to 11, but using using the Camden and Islington pathway

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	ANGERS	Angers	France	49000
2	CHU Angers	Angers	France	49000
3	BECON	Bécon-les-Granits	France	49370
4	Chalonnes	Chalonnes-sur-Loire	France	49290
5	Montreuil	Montreuil-Bellay	France	49260
6	SEGRE	Segré	France	49500