Circulating Thrombospondin-2 as a Novel Fibrosis Biomarker of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes

Abstract

Objective <br>Preclinical studies suggested thrombospondin-2 (TSP2) to be implicated in liver fibrosis. However, the clinical relevance of TSP2 in non-alcoholic fatty liver disease (NAFLD) remains undefined. Here, we investigated the cross-sectional and longitudinal associations of circulating TSP2 levels with advanced fibrosis (≥F3 fibrosis) in NAFLD. <br> <br>Research Design & Methods <br>Serum TSP2 levels were measured in 820 patients comorbid with type 2 diabetes and NAFLD. All participants received vibration controlled transient elastography (VCTE) at baseline to evaluate their hepatic steatosis and fibrosis using controlled attenuation parameter (CAP) and liver stiffness (LS) measurements, respectively. Among those without advanced fibrosis at baseline, reassessment VCTE was performed to determine if ≥F3 fibrosis had developed over time. Multivariable logistic regression analysis was used to evaluate the cross-sectional and longitudinal associations of serum TSP2 level with ≥F3 fibrosis. <br> <br>Results <br>Baseline serum TSP2 level was independently associated with the presence of ≥F3 fibrosis (OR 5.13, p<0.001). The inclusion of serum TSP2 level significantly improved the identification of ≥F3 fibrosis by clinical risk factors. Over a median follow-up of 1.5 years, 8.8% developed ≥F3 fibrosis. Baseline serum TSP2 level was significantly associated with incident ≥F3 fibrosis (OR 2.82, p=0.005), independent of other significant clinical risk factors of fibrosis progression including body mass index, platelet count and CAP at baseline. <br> <br>Conclusion <br>Circulating TSP2 level was associated with both the presence and development of advanced fibrosis, and might be a potentially useful prognostic biomarker for the development and progression of liver fibrosis in NAFLD patients with type 2 diabetes.