ELF score: A validated serum test strongly predictive of fibrosis in SSc

Background. The absence of a serum test predictive of activity or severity in Scleroderma (SSc) is a major burden both for clinical intervention studies and for clinical management. Recently, a large multicentre study has identified an algorithm of three serum biomarkers as predictive of severity and clinical outcome in chronic liver disease. The algorithm, known as Enhanced Liver Fibrosis (ELF), includes the measurement of serum concentrations of hyaluronic acid, TIMP-1 and aminoterminal propeptide of procollagen Type III. Objective. To evaluate the predictive value of ELF test as surrogate outcome measure of fibrosis in SSc. Methods. A total of 210 SSc patients were enrolled in the study. All patients were investigated for clinical and serological subset, disease duration (d.d.), vascular, skin, joint, tendon, muscle, oesophagogastrointestinal, lung, heart and kidney involvement, disease severity, disease activity and HAQ-DI. ELF score was determined blindly by an independent commercial service (iQur, London, UK). Correlations were calculated using Spearman's correlation test. Mann-Whitney test was used to perform comparison between groups. All the variables found to be correlated in univariate analysis were subsequently assessed by step-wise regression analysis. Data were analysed using SPSS18 software. Results. The mean ELF score in SSc patients sera was 8.71 (1). ELF score significantly correlated with: mRSS (r=0.28; P<0.0001), FVC (r=-0.16; P=0.0287), DLCO (r=-0.32; P<0.0001), EScSG-Activity Index (r=0.23; P=0.02), total Medsger's disease severity score (r=0.3; P<0.0001) and severity score of skin (r=0.31; P<0.0001), joint/tendon (r=0.23; P=0.0007), muscle (r=0.27; P<0.0001), GI tract (r=0.17; P=0.0144), heart (r=0.22; P=0.0011), HAQ-DI (r=0.32; P<0.00001), ESR (r=0.25; P=0.0003), age (r=0.41; P<0.0001). Step-wise regression analysis identified mRSS (standardized b=0.299, P<0.0001), age (standardized b=0.289, P=0.001), DLCO (standardized b=-0.245, P=0.004) and gender (standardized b=0.235, P=0.005) as independently associated with ELF score. The median ELF score was significantly higher in patients with dcSSc enrolled within the first year of the disease than in age-/gendermatched lcSSc patients with >5 years d.d. (P=0.0152) and not significantly higher when compared with matched dcSSc with >3 years d.d. The median ELF score was higher in SSc patients with chest HRCT fibrosis and DLCO-FVC <80% predicted value, than in SSc controls matched for age, gender, subset, mRSS and d.d. (P=0.0079). Conclusion. The ELF test is a simple serum test that significantly correlates with several measures of fibrosis in SSc. It has a clear face validity for measuring the concentration of molecules involved in extracellular matrix turnover and correlates with fibrotic severity and activity in SSc. ELF test should be considered as outcome measure in clinical trials.