title: The enhanced liver fibrosis test: a clinical grade, validated serum test, biomarker of overall fibrosis in systemic sclerosis.
abstract: OBJECTIVE
  The absence of a serological surrogate outcome measure of fibrosis in systemic sclerosis (SSc) is a major deficiency for intervention studies and clinical management. An algorithm including the serum concentration of procollagen-III aminoterminal-propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid, has recently been validated as predictive of severity and clinical outcome in chronic liver diseases (enhanced liver fibrosis (ELF) test) and implemented as a clinical grade test available for physicians. We evaluated the ELF test as a surrogate outcome measure in SSc.
  
  
  METHODS
  The ELF score was determined blindly in 210 patients with SSc. Results were correlated with clinical, functional and instrumental variables including disease severity, activity and disability.
  
  
  RESULTS
  The ELF test was above normal range in 83% of SSc patients (175/210). The ELF score showed a significant correlation (p<0.0001) with extent of skin involvement (r=0.28), diffusing lung capacity of carbon monoxide (DLCO) (r=-0.32), health assessment questionnaire-disability index (HAQ-DI) (r=0.32), disease severity score (r=0.3) and age (r=0.41). In addition, ELF correlated with disease activity (r=0.23; p=0.02). Using regression analysis, the extent of skin involvement, age, DLCO and gender were independently associated with the ELF score. The ELF score did not correlate with the presence of pulmonary artery hypertension, digital ulcers or any other measure of vasculopathy.
  
  
  CONCLUSIONS
  The ELF test is a clinical-grade serum test that significantly correlates with several measures of fibrosis in SSc and with overall disease activity, severity and HAQ-DI. The specific correlation with fibrosis and its face validity, together with the feasibility of the test, warrant its further development as a surrogate outcome measure of fibrosis in SSc.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, , Leeds, UK.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Abignano
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cuomo
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
authors.forename: William M
authors.initials: WM
authors.lastname: Rosenberg
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Francesco
authors.initials: F
authors.lastname: Del Galdo
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000175:diagnosis / Q000209:etiology; D012595:Scleroderma, Systemic / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers