Written informed consent was obtained from all subjects at the time of health check-up, and the study was conducted in accordance with the Helsinki Declaration. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin-A was measured by ELISA. IMT was assessed using a high-resolution ultrasound Vismodegib mouse scanner. Using recombinant human fetuin-A, we investigated the effects of fetuin-A on HSCs. 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). Next, we analyzed the correlation between the serum fetuin-A level and mean IMT in four groups segmented by mean IMT value quartile (range of mean IMT; group 1: <0.7, group 2: 0.7-0.8, group 3: 0.8-1.0, group 4: 1 mm). Interestingly, the serum fetuin-A level did not change in the three normal groups, but significantly decreased only in the
abnormal group (mean IMT ≥ 1 mm). Multivariate analysis revealed that fetuin-A concentration was a significant and independent determinant of platelet count, NAFLD fibrosis score, and mean IMT. Recombinant fetuin-A suppressed TGF-β1 signaling and fibrosis-re-lated 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 Stem Cell Compound Library cell assay markers in NAFLD patients. Circulating fetuin-A could be a useful
serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients. Disclosures: Tetsuo Takehara – Grant/Research Support: Chugai Pharmaceutical Co., MSD K.K. The following people have nothing to disclose: Yoshihiro Kamada, Motoya Sato, Yuri Takeda, Sachiho KIda, Yuka Ohara, Hironobu Fujii, Maaya Akita, Kayo Mizutani, Yuichi Yoshida, Makoto Yamada, Hidetaka Hougaku, Eiji Miyoshi Background. The diagnosis and staging of NASH still relies on liver histology. However, histological classifications of NAFLD 上海皓元 are based on morphology, thus empirical, with undetermined clinical relevance and correlates. Aim. To investigate whether different histological categories according to the FLIP algorithm and the SAF score reflect distinct patient profiles and are predicted by relevant clinical/biological features. Methods. 140 liver biopsies of patients (pts) with suspected NAFLD based on metabolic risk factors (cohort 1) and 78 liver biopsies from a multicentric therapeutic trial of ASP9831 in NASH (cohort 2) were reassessed with the FLIP algorithm (identifying NASH and non-NASH, NAFL) and the SAF score (S=Steatosis; A=Activity; F=Fibrosis; Hepatology 2012;56:1751, identifying histolog-ically severe forms, HSF, as A≥3 and/or F≥3) by a single liver pathologist, blinded to clinical data. Results. In cohort 1, 60 pts (43%) were diagnosed with NASH according to the FLIP algorithm.