• Jérôme Boursier, Maeva Guillaume, Vincent Leroy, Marie Irlès, Marine Roux, Adrien Lannes, Juliette Foucher, Floraine Zuberbuhler, Cyrielle Delabaudière, Justine Barthelon, Sophie Michalak, Jean-Baptiste Hiriart, Jean-Marie Peron, Theophile Gerster, Brigitte Le Bail, Jeremie Riou, Gilles Hunault, Wassil Merrouche, Frederic Oberti, Laurence Pelade, Isabelle Fouchard, Christophe Bureau, Paul Calès, and Victor de Ledinghen.
• Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France; Laboratoire HIFIH, UPRES 3859, SFR 4208, Université d'Angers, Angers, France. Electronic address: JeBoursier@chu-angers.fr.
• J. Hepatol. 2019 Aug 1; 71 (2): 389-396.

Background & AimsAdvanced 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.MethodsA 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.ResultsFor the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840 ± 0.013, p ≤0.005). FibroMeter was the most accurate blood test (AUROC: 0.793 ± 0.015, p ≤0.017). The combinatory test FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866 ± 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.ConclusionThe 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 SummaryThe 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.Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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