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Objective: Baseline circulating thrombospondin‐2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography. Design: Serum TSP2 levels were measured in participants from a randomized, open‐label intervention study, at baseline and after 24‐weeks treatment of either dapagliflozin 10 mg (N = 30) or sitagliptin 100 mg daily (N = 30). Vibration‐controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively. Patients and Measurements: Among all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p =.012), CAP (p =.015) and LS (p =.011) after 24 weeks. Results: Serum TSP2 level decreased significantly from baseline in dapagliflozin‐treated participants (p =.035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (r =.487, p =.006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment. Conclusions: Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: 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, we investigated the cross-sectional and longitudinal associations of circulating TSP2 levels with advanced fibrosis (F3 or greater [≥FE] fibrosis) in NAFLD.Research Design and Methods: 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 ≥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.Results: Baseline serum TSP2 level was independently associated with the presence of ≥F3 fibrosis (odds ratio [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 BMI, platelet count, and CAP at baseline.Conclusions: 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. [ABSTRACT FROM AUTHOR]