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Type: Journal article
Title: Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis
Author: McPherson, S.
Hardy, T.
Dufour, J.
Petta, S.
Romero-Gomez, M.
Allison, M.
Oliveira, C.
Francque, S.
van Gaal, L.
Schattenberg, J.
Tiniakos, D.
Burt, A.
Bugianesi, E.
Ratziu, V.
Day, C.
Anstee, Q.
Citation: American Journal of Gastroenterology, 2017; 112(5):740-751
Publisher: Nature
Issue Date: 2017
ISSN: 0002-9270
Statement of
Stuart McPherson, Tim Hardy, Jean-Francois Dufour, Salvatore Petta, Manuel Romero-Gomez, Mike Allison, Claudia P. Oliveira, Sven Francque, Luc Van Gaal, Jorn M. Schattenberg, Dina Tiniakos, Alastair Burt, Elisabetta Bugianesi, Vlad Ratziu, Christopher P. Day and Quentin M. Anstee
Abstract: Objectives: Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD. Methods: Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (n=74), 36–45 (n=96), 46–55 (n=197), 56–64 (n=191), and ≥65 years (n=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3–F4) for each group was assessed using liver biopsy as the standard. Results: Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77%; NFS 0.12, sensitivity 80%). Conclusions: The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue.
Keywords: Liver
Liver Cirrhosis
Alanine Transaminase
Aspartate Aminotransferases
False Positive Reactions
Platelet Count
Area Under Curve
Predictive Value of Tests
ROC Curve
Age Factors
Reference Values
Middle Aged
Non-alcoholic Fatty Liver Disease
Rights: © The Author(s) 2017 This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
DOI: 10.1038/ajg.2016.453
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