Supporting data for "Thrombospondin-2 as a Novel Biomarker of Metabolic Associated Steatohepatitis and Hepatic Fibrosis: from Noninvasive Disease Severity Stratification towards Therapeutic Interventions"

Nonalcoholic fatty liver disease (NAFLD), the chronic hepatic manifestation closely linked to metabolic syndrome (MetS), has recently been renamed as metabolic associated fatty liver disease (MAFLD). A pathophysiological heterogeneous disease with “multiple hits” driving its progression, MAFLD comprises a spectrum of liver disorders featured with metabolic associated fatty liver, metabolic associated steatohepatitis (MASH), fibrosis, cirrhosis, and liver cancer. With high prevalence and clinical importance of MAFLD, currently there are two main challenges in its diagnosis and management. One is the lack of noninvasive and cost-effective diagnostic tool for MAFLD severity stratification, especially for differentiating MASH from simple steatosis and staging liver fibrosis. Another is no regulatory approved drug available for treatment of MASH/NASH.  

From this study, serum thrombospondin-2 has been found closely associated with the severity of MetS, MAFLD and liver fibrosis, which could be a promising noninvasive biomarker for differentiating MASH/NASH from simple steatosis. High serum thrombospondin-2 level had high diagnostic accuracy for identifying at-risk MASH patients, who are candidates for pharmacotherapeutic clinical trials. 

In this study, recombinant thrombospondin-2 proteins with biological activities have been expressed. Polyclonal anti-thrombospondin-2 neutralizing antibodies have been developed and the preclinical therapeutic effects have been established. As proof-of-concept, the first evidence has been provided that antibody-mediated neutralization of thrombospondin-2  representing a promising therapeutic strategy for MASH and hepatic fibrosis. 

Collectively, thrombospondin-2 is a highly promising noninvasive biomarker and therapeutic target of MASH/NASH and hepatic fibrosis.