Fetuin‐A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects. (26th February 2014) - Sato, Motoya
Abstract Background & Aims Fetuin‐A (α2HS‐glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)‐β1 signalling inhibitor. Serum fetuin‐A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin‐A as a predictive fibrosis biomarker in NAFLD patients remains unclear. In this study, we investigated the relationship between circulating fetuin‐A levels and fibrosis‐related markers [platelet count, NAFLD fibrosis score and carotid intima media thickness (IMT)] in subjects with NAFLD. Methods A total of 295 subjects (male, 164; female, 131) who received medical health check‐ups were enrolled in this study. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin‐A was measured by ELISA. IMT was assessed using a high‐resolution ultrasound scanner. Using recombinant human fetuin‐A, we investigated the effects of fetuin‐A on hepatic stellate cells, which play a pivotal role in the process of hepatic fibrosis. Results Serum fetuin‐A concentration was significantly correlated with platelet count (R = 0.19, P < 0.01), NAFLD fibrosis score (R = −0.25, P < 0.01) and mean IMT (R = −0.22, P < 0.01). Multivariate analyses revealed that the fetuin‐A concentration is a significant and independent determinant of platelet count, NAFLD fibrosis score and mean IMT. Recombinant fetuin‐A suppressed TGF‐β1 signalling and fibrosis‐related gene expression and increased the expression of TGF‐β1 pseudoreceptor bone morphogenic protein and activin membrane‐bound inhibitor (BAMBI). Conclusions Serum fetuin‐A level is associated with liver/vessel fibrosis‐related markers in NAFLD patients. Circulating fetuin‐A could be a useful serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients.