title: Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity.
abstract: Non-alcoholic fatty liver disease (NAFLD) is common in diabetes and obesity but few have clinically significant liver fibrosis. Improved risk-assessment is needed as the commonly used clinical-risk algorithm, the NAFLD fibrosis score (NFS), is often inconclusive.
  
  
  OBJECTIVE
  To determine whether circulating fibroblast activation protein (cFAP), which is elevated in cirrhosis, has value in excluding significant fibrosis, particularly combined with NFS.
  
  
  METHODS
  cFAP was measured in 106 with type 2 diabetes who had transient elastography (Cohort 1) and 146 with morbid obesity who had liver biopsy (Cohort 2).
  
  
  RESULTS
  In Cohort 1, cFAP (per SD) independently associated with median liver stiffness (LSM) ≥ 10.3 kPa with OR of 2.0 (95% CI 1.2-3.4), p=0.006. There was 0.12 OR (95% CI 0.03-0.61) of LSM ≥ 10.3 kPa for those in the lowest compared with the highest FAP tertile (p=0.010). FAP levels below 730 pmol AMC/min/mL had 95% NPV for LSM ≥ 10.3 kPa and reclassified 41% of 64 subjects from NFS 'indeterminate-risk' to 'low-risk'. In Cohort 2, cFAP (per SD), associated with 1.7 fold (95% CI 1.1-2.8) increased odds of significant fibrosis (F ≥ 2), p=0.021, and low cFAP reclassified 49% of 73 subjects from 'indeterminate-risk' to 'low-risk'.
  
  
  CONCLUSIONS
  Lower cFAP, when combined with NFS, may have clinical utility in excluding significant fibrosis in diabetes and obesity.
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; The Charles Perkins Centre, Building D17, Johns Hopkins Drive, The University of Sydney, NSW, Australia; NHMRC Clinical Trials Centre, The University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia. Electronic address: kath.williams@sydney.edu.au.
authors.forename: K H
authors.initials: KH
authors.lastname: Williams
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: anajulia.vribeiro@gmail.com.
authors.forename: A J
authors.initials: AJ
authors.lastname: Viera de Ribeiro
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: e_prakoso@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Prakoso
authors.affiliation: NHMRC Clinical Trials Centre, The University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia. Electronic address: annesophie.veillard@sydney.edu.au.
authors.forename: A S
authors.initials: AS
authors.lastname: Veillard
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: n.shackel@centenary.usyd.edu.au.
authors.forename: N A
authors.initials: NA
authors.lastname: Shackel
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: koko_bu@hotmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; Sydney Nursing School, Building M02, The University of Sydney, NSW 2006, Australia. Electronic address: belinda.brooks@sydney.edu.au.
authors.forename: B
authors.initials: B
authors.lastname: Brooks
authors.affiliation: Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia. Electronic address: erikacavanagh@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Cavanagh
authors.affiliation: Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia. Electronic address: liz.jim.raleigh@bigpond.com.
authors.forename: J
authors.initials: J
authors.lastname: Raleigh
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; The Charles Perkins Centre, Building D17, Johns Hopkins Drive, The University of Sydney, NSW, Australia. Electronic address: sue.mclennan@sydney.edu.au.
authors.forename: S V
authors.initials: SV
authors.lastname: McLennan
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: G.McCaughan@centenary.usyd.edu.au.
authors.forename: G W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: Sackler School of Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. Electronic address: william.bachovin@tufts.edu.au.
authors.forename: W W
authors.initials: WW
authors.lastname: Bachovchin
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: f.keane@centenary.org.au.
authors.forename: F M
authors.initials: FM
authors.lastname: Keane
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Sydney, NSW 2052, Australia; The St George Hospital, Gray Street, Kogarah, NSW 2217, Australia. Electronic address: a.zekry@unsw.edu.au.
authors.forename: A
authors.initials: A
authors.lastname: Zekry
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; The Charles Perkins Centre, Building D17, Johns Hopkins Drive, The University of Sydney, NSW, Australia. Electronic address: stephen.twigg@sydney.edu.au.
authors.forename: S M
authors.initials: SM
authors.lastname: Twigg
authors.affiliation: Sydney Medical School, The Edward Ford Building (A27), The University of Sydney, NSW, Australia; Centenary Institute, Locked Bag 6, Newtown, NSW 2042, Australia. Electronic address: m.gorrell@centenary.org.au.
authors.forename: M D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D000328:Adult; D000954:Antigens, Surface; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D054459:Elasticity Imaging Techniques; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D018093:Gelatinases / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D009767:Obesity, Morbid / Q000150:complications*; D012697:Serine Endopeptidases / Q000097:blood*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000954:Antigens, Surface; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: Biomarker; Fibroblast activation protein; NAFLD fibrosis score