Circulating Thrombospondin-2 as a Novel Fibrosis Biomarker o
Preclinical studies have suggested that thrombospondin-2 (TSP2) is implicated in liver fibrosis. However, the clinical relevance of TSP2 in nonalcoholic fatty liver disease (NAFLD) remains undefined. Here, this study investigated the cross-sectional and longitudinal associations of circulating TSP2 levels with advanced fibrosis (F3 or greater fibrosis) in NAFLD.

Serum TSP2 levels were measured in 820 patients 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 whether more than 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 more than F3 fibrosis.

-- Baseline serum TSP2 level was independently associated with the presence of more than F3 fibrosis.

-- The inclusion of serum TSP2 level significantly improved the identification of more than F3 fibrosis by clinical risk factors.

-- Over a median follow-up of 1.5 years, 8.8% developed more than F3 fibrosis.

-- Baseline serum TSP2 level was significantly associated with incident more than F3 fibrosis, independent of other significant clinical risk factors of fibrosis progression, including BMI, platelet count, and CAP at baseline.

Conclusively, circulating TSP2 level was associated with both the presence and the development of advanced fibrosis and might be a potentially useful prognostic biomarker for the development and progression of liver fibrosis in patients with type 2 diabetes and NAFLD.