Serum Thrombospondin-2 Levels Associated with MAFLD Severity

Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease (NAFLD), has emerged as the most common cause of liver disease globally. 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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