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Aliment Pharmacol Ther. 2017 Sep;46(6):617-627. doi: 10.1111/apt.14219. Epub 2017 Jul 27.

Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD.

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Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, France.
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy.
INSERM U1053, Bordeaux University, Bordeaux, France.
Service de Pathologie, Hôpital Pellegrin, Bordeaux University Hospital, Bordeaux, France.



The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited.


To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients.


We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan.


LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%.


The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD.

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