Performance of Simple Fibrosis Scores in Nonobese Patients With Nonalcoholic Fatty Liver Disease.

Because only a minority of patients with nonalcoholic fatty liver disease (NAFLD) have advanced fibrosis and would eventually develop liver-related complications, current guidelines recommend initial assessment with noninvasive tests of fibrosis.1-3 Most previous studies focused on overweight and obese patients. Despite a strong association between obesity and NAFLD, 3%-30% of people with relatively normal body mass index (BMI) may still have NAFLD.4,5 Hence, this study aims to evaluate the performance of the common noninvasive tests in non-obese (BMI <25 kg/m2) and obese (BMI ≥25 kg/m2) NAFLD patients.

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.

Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease.

OBJECTIVE: The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis. DESIGN: We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy. RESULTS: 391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75-0.88 for F2-4, 0.83-0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe. CONCLUSION: High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.