Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral

Abstract

We evaluated the value of secreted glycoprotein thrombospondin-2 (TSP-2) to predict hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C (CHC) patients after Hepatitis C virus (HCV) elimination by direct-acting antiviral agents (DAAs). A total of 786 CHC patients without an HCC history who achieved a sustained virological response (SVR) with DAAs were randomly assigned 2:1, with 524 patients as the derivation cohort and 262 patients as the validation cohort. Serum TSP-2 levels at the end of treatment were measured by enzyme-linked immunosorbent assay (ELISA). In the derivation cohort, the cumulative HCC rate was significantly higher in the high TSP-2 group than in the low TSP-2 group. Multivariate Cox proportional hazards analysis revealed that TSP-2, α-fetoprotein (AFP), and the fibrosis-4 (FIB-4) index were independent HCC risk factors. The area under the receiver operating characteristic curve (AUROC) of the score calculated from these three factors (AFT score) for predicting HCC was 0.83, which was significantly higher than that of each factor alone (TSP-2: 0.70, AFP: 0.72, FIB-4: 0.69). The AFT score was used to stratify patients according to the risk of HCC occurrence in the validation cohort. Lastly, in patients with a FIB-4 index < 3.25, the serum TSP-2 levels could be used to identify those patients with a high risk of HCC occurrence. Serum TSP-2 levels are a predictive biomarker of HCC occurrence in CHC patients after HCV elimination by DAA treatment. The AFT score using TSP-2, AFP, and the FIB-4 index may identify those who require HCC surveillance.

Thrombospondin 2 is a key determinant of fibrogenesis in NAFLD

“…These results were supported by a large investigation of NAFLD patients with diabetes mellitus or metabolic-associated fatty liver disease (17,18). Furthermore, a correlation between the degree of fibrosis and inflammation and serum TSP2 levels was observed not only in NAFLD, but also in hepatitis C virus -infected patients (19,20). Despite these advances, however, the specific liver cell populations responsible for THBS2/TSP2 expression in NAFLD, the underlying mechanisms governing expression dynamics, and the precise role of THBS2/TSP2 in the pathogenesis of NAFLD remain largely unknown.…”

Thrombospondin-2 as a potential noninvasive biomarker of hepatocyte injury but not liver fibrosis in children with MAFLD: A preliminary study

“…A study of adult patients with NAFLD and type 2 diabetes showed that serum TPS2 levels were associated not only with obesity-related liver fibrosis, but also with the development of advanced fibrosis in subsequent years [23]. A recent analysis showed the utility of serum TSP2 as a predictive marker of fibrosis stage and hepatocellular carcinoma occurrence in patients with chronic hepatitis after hepatitis C virus (HCV) elimination [24]. Similarly, Iwadare et al showed that TSP2 levels correlate with liver fibrosis stage in HCV-infected patients [25].…”

Thrombospondin 2 is a key determinant of fibrogenesis in non‐alcoholic fatty liver disease

“…17,18 Furthermore, a correlation between the degree of fibrosis and inflammation and serum TSP2 levels was observed not only in NAFLD, but also in hepatitis C virus-infected patients. 19,20 Despite these advances, however, the specific liver cell populations responsible for THBS2/TSP2 expression in NAFLD, the underlying mechanisms governing expression dynamics, and the precise role of THBS2/TSP2 in the pathogenesis of NAFLD remain largely unknown.…”