Serum Thrombospondin-2 Levels Associated with MAFLD Severity

With the expanding epidemic of obesity worldwide, MAFLD is becoming an increasingly burdensome condition, both clinically and economically.

Thrombospondins are a family of multidomain and secretory glycoproteins. Among them, thrombospondin 2 (TSP2) encoded by the TSP2 gene has been reported to be involved in various functions such as collagen/fibrin formation, maintenance of normal blood vessel density and cell adhesion properties.

A large team of medical scientists from The University of Hong Kong (Hong Kong, China) and their colleagues investigated the associations of serum thrombospondin-2 (TSP2) with obesity-related metabolic syndrome (MetS) and MAFLD severity, and the potential diagnostic value of serum TSP2 for identifying at-risk metabolic associated steatohepatitis (at-risk MASH).

The team collected blood samples, clinical data, and liver biopsies from consecutively recruited 252 individuals with morbid obesity receiving bariatric surgery. Histopathologies of liver biopsies were examined in a blinded fashion by three independent pathologists. Serum TSP2 levels were measured by enzyme-linked immunosorbent assay (ELISA).

The scientists reported that serum TSP2 levels were significantly elevated in MetS (1.58 [1.07-2.20] ng/mL) compared with non-MetS (1.28 [0.84-1.73] ng/mL) in obese patients and positively correlated with increasing number of the MetS components, fasting glucose, HbA1c, fasting insulin, C-peptide, HOMA-IR after adjustment of conventional confounders.

Serum TSP2 levels differentiated MASH (1.74 [1.32-3.09] ng/mL) from the other non-MASH less severe groups normal liver (1.41 [1.04-1.63] ng/mL), simple steatosis (1.45 [0.89-1.92] ng/mL) and borderline MASH (1.30 [0.99-2.17] ng/mL). Elevated serum TSP2 was positively associated with the severity of hepatic steatosis, inflammation, fibrosis, and abnormal liver function independent of age, sex and adiposity. Furthermore, high serum TSP2 identified at-risk MASH with AUC of 0.84.

The authors concluded that serum TSP2 is closely associated with severity and progression of MetS and MAFLD, and is a promising noninvasive biomarker for differentiating MASH from benign steatosis and identifying at-risk MASH patients among individuals with obesity. The study was published on May 9, 2022 in The Journal Of Clinical Endocrinology And Metabolism.

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