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. 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.