Comparison of Two sTRAtegies For the Non-Invasive Diagnosis of advanCed Liver Fibrosis in NAFLD
Comparison of Two sTRAtegies For the Non-Invasive Diagnosis of advanCed Liver Fibrosis in NAFLD
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
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.
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