title: Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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%).
  
  
  
  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.
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: McPherson
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Hardy
authors.affiliation: University Clinic for Visceral Surgery and Medicine, University of Berne, Berne, Switzerland.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.affiliation: UCM Digestive Diseases, Hospital Universitario Virgen Macarena-Virgen del Rocío, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.affiliation: Liver Unit, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Cambridge, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Allison
authors.affiliation: Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Oliveira
authors.affiliation: Department of Gastroenterology Hepatology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.affiliation: Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.affiliation: Department of Medicine, University Hospital, Mainz, Germany.
authors.forename: Jörn M
authors.initials: JM
authors.lastname: Schattenberg
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Dina
authors.initials: D
authors.lastname: Tiniakos
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Alastair
authors.initials: A
authors.lastname: Burt
authors.affiliation: Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Quentin M
authors.initials: QM
authors.lastname: Anstee
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood*; D001706:Biopsy; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D010976:Platelet Count; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase