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. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Williams, K.H.; Viera de Ribeiro, A.J.; Prakoso, E.; Veillard, A.S.; Shackel, N.A.; Bu, Y.; Brooks, B.; Cavanagh, E.; Raleigh, J.; McLennan, S.V.; McCaughan, G.W.; Bachovchin, W.W.; Keane, F.M.; Zekry, A.; Twigg, S.M.; Gorrell, M.D.
• Is Part Of: Diabetes research and clinical practice. Volume 108:Issue 3(2015)
• Page Start: 466
• Page End: 472
• Publication Date: 2015-06
• Subjects: NAFLD fibrosis score -- Fibroblast activation protein -- Biomarker; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2015.02.024
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Many patients with diabetes/obesity and NAFLD have significant liver fibrosis. Circulating biomarkers to exclude liver fibrosis in NAFLD are required. A low serum FAP level in such patients can help to exclude severe liver fibrosis. 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. Aims: 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.