New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD.

BACKGROUND & AIMS: Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. Here, we aimed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD. METHODS: A total of 938 patients with biopsy-proven NAFLD were randomized 2:1 into derivation and validation sets. All patients underwent liver stiffness measurement with vibration controlled transient elastography (VCTE) and blood fibrosis tests (NAFLD fibrosis score, Fibrosis-4 [FIB4], Fibrotest, Hepascore, FibroMeter). FibroMeterVCTE, which combines VCTE results and FibroMeter markers in a single test, was also calculated in all patients. RESULTS: For the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840 ±â€¯0.013, p ≤0.005). FibroMeter was the most accurate blood test (AUROC: 0.793 ±â€¯0.015, p ≤0.017). The combinatory test FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866 ±â€¯0.012, p ≤0.005). The sequential combination of FIB4 then FibroMeterVCTE (FIB4-FMVCTE algorithm) or VCTE then FibroMeterVCTE (VCTE-FMVCTE algorithm) provided an excellent diagnostic accuracy of 90% for advanced fibrosis, with liver biopsy only required to confirm the diagnosis in 20% of cases. The FIB4-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed. CONCLUSION: The sequential combination of fibrosis tests in the FIB4-FMVCTE and VCTE-FMVCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD. These algorithms should now be validated for the diagnosis of advanced liver fibrosis in diabetology or primary care settings. LAY SUMMARY: The evaluation of liver fibrosis is mandatory in non-alcoholic fatty liver disease (NAFLD), as advanced fibrosis identifies the subgroup of patients with impaired prognosis. FibroMeterVCTE is a new fibrosis test combining blood markers and the result of vibration controlled transient elastography (VCTE) into a single diagnostic test. Our results show that FibroMeterVCTE outperforms other blood fibrosis tests and VCTE alone for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 patients with biopsy-proven NAFLD. Sequential algorithms using a simple blood test or VCTE as a first-line procedure, then FibroMeterVCTE as a second-line test accurately classified 90% of patients.

Simple blood fibrosis tests reduce unnecessary referrals for specialized evaluations of liver fibrosis in NAFLD and ALD patients.

BACKGROUND: Liver fibrosis evaluation is mandatory in non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) to decide the patient management. Patients with these diseases are usually under the care of non-liver specialists who refer them to specialized centers where the most accurate fibrosis tests are available. We aimed to evaluate whether simple blood fibrosis tests available to all physicians help to reduce the rate of unnecessary referral of NAFLD and ALD patients without advanced fibrosis. METHODS: NAFLD and/or ALD patients newly referred to our center for a non-invasive evaluation of liver fibrosis were retrospectively included. The FibroMeterVCTE (FMVCTE, combination of blood markers and Fibroscan results) was defined as the reference test for specialized evaluation of liver fibrosis. A FMVCTE result <0.384 indicated the absence of advanced fibrosis and thus an "unnecessary referral". RESULTS: 558 patients were included (NAFLD: 283, ALD: 156, mixed NAFLD+ALD: 119). FMVCTE was <0.384 (unnecessary referral) in 58.8% of patients. FIB4 was <1.30 in 45.2% and eLIFT <8 in 47.7% of the patients. 84.9% of patients with FIB4 <1.30 and 85.3% of patients with eLIFT <8 had also FMVCTE <0.384. Therefore, using FIB4 or eLIFT as first-line evaluation of liver fibrosis decreased by three-fold the rate of unnecessary referral. The negative predictive value of FIB4 and eLIFT was >80% whatever the underlying cause of chronic liver disease. CONCLUSION: The use of eLIFT by non-liver specialists for NAFLD and ALD patients can improve the relevance of referrals for specialized evaluation of liver fibrosis.

Noninvasive diagnosis of liver fibrosis in NAFLD: Tips tricks.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent, affecting 25% of the general population. Liver fibrosis must be accurately evaluated in NAFLD to determine the severity of the disease and establish patient management. We present the case of a patient with diabetes showing minimal perturbations of liver function tests, but for whom a simple blood fibrosis test suggested the presence of advanced liver fibrosis. The patient was referred to a hepatologist who confirmed the diagnosis using a specialized blood test and transient elastography. Thereafter, a liver biopsy was performed and pathology was positive for cirrhosis. An upper gastrointestinal endoscopy showed no gastrointestinal varices. Simple blood fibrosis tests are very attractive for the first-line evaluation of liver fibrosis by non-specialists in the large populations of NAFLD and diabetic patients, as they are inexpensive, easy to perform, and accurate for the exclusion of advanced liver fibrosis. Non-specialists must however use them appropriately to avoid unnecessary over-referral to hepatologists. These latter can confirm the diagnosis of advanced liver fibrosis via agreement between a specialized blood test and liver elastography. In addition to the diagnosis of liver fibrosis, noninvasive tests are now recommended for the screening of gastrointestinal varices at risk of bleeding. Liver elastography must be interpreted by a specialist because the choice of the probe, the quality of the examination, and many conditions other than liver fibrosis can influence the examination and create a risk of false positives. Noninvasive tests of liver fibrosis have enabled exciting possibilities for widespread screening of advanced forms of chronic liver diseases. This will become particularly relevant in NAFLD when drugs currently in therapeutic trials become available in the next few years.

Liver Stiffness Measurement With FibroScan: Use the Right Probe in the Right Conditions!

INTRODUCTION: FibroScan's M and XL probes give significantly different results, which could lead to misevaluation of liver fibrosis if the correct probe is not chosen. According to the manufacturer, the M probe should be used when the skin-liver capsule distance (SCD) is <25 mm, and the XL probe should be used when SCD is ≥25 mm. We aimed at validating this recommendation and defining the conditions of use for FibroScan probes in clinical practice. METHODS: Four hundred thirty-nine patients with biopsy-proven chronic liver disease were included. Of them, 382 had successful examinations with both M and XL probes. Advanced fibrosis was defined as Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) F ≥3 or Metavir F ≥2. RESULTS: In a same patient, XL probe results were significantly lower than M probe results: 7.9 (5.6-11.7) vs 9.5 (6.7-14.6) kPa, respectively (P < 0.001). After matching for age, sex, liver fibrosis, and serum transaminases, M probe results in patients with SCD <25 mm and XL probe results in those with SCD ≥25 mm did not significantly differ: 8.8 (6.0-12.0) vs 9.1 (6.7-12.8) kPa, respectively (P = 0.175). Of note, 81.4% of patients with body mass index (BMI) <32 kg/m had SCD <25 mm, and 77.7% of patients with BMI ≥32 kg/m had SCD ≥25 mm. A practical algorithm using BMI first and then the FibroScan Automatic Probe Selection tool was proposed to help physicians accurately choose which probe to use in clinical practice. CONCLUSIONS: There is no significant difference in results between M and XL probes when they are used in the right conditions. In clinical practice, the probe should be selected according to the BMI and the Automatic Probe Selection tool.

Direct comparison of the specialised blood fibrosis tests FibroMeterV2G and Enhanced Liver Fibrosis score in patients with non-alcoholic fatty liver disease from tertiary care centres.

BACKGROUND: The Enhanced Liver Fibrosis score (ELF) and the FibroMeterV2G are two specialized blood fibrosis tests which include direct markers of liver fibrosis. They have been shown to be more accurate than the simple blood fibrosis tests FIB4 and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). AIMS: To directly compare the accuracies of ELF and FibroMeterV2G for the non-invasive diagnosis of liver fibrosis in NAFLD. METHODS: Four hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeterV2G , NFS, and FIB4. Advanced fibrosis F3/4 on liver biopsy (NASH CRN scoring) was the primary endpoint. RESULTS: Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeterV2G (0.804 ± 0.021) had significantly higher AUROC than NFS (0.722 ± 0.025, P < .010) and FIB4 (0.739 ± 0.024, P < .020). AUROC for advanced fibrosis and Obuchowski index were not significantly different between ELF and FibroMeterV2G . Algorithms using first ELF or FibroMeterV2G and then liver biopsy in case of undetermined diagnosis provided high diagnostic accuracy for advanced fibrosis: 90% sensitivity, 90% specificity, 93% negative predictive value, 85% positive predictive value, and 90% correct classification. In these algorithms, the rate of liver biopsy was 45.3% with ELF versus 39.3% with FibroMeterV2G (P = .065). CONCLUSIONS: ELF and FibroMeterV2G have equal accuracy and perform better than the simple FIB4 and NFS tests for the non-invasive diagnosis of advanced liver fibrosis in patients with NAFLD from tertiary care centres.