Mo1840 Serum Levels of Apoptosis Inhibitor of Macrophage (AIM) are Associated With Hepatic Fibrosis and Insulin Resistance in Patients With Hepatitis C Virus-Associated Liver Disease

Abstract

Background: Apoptosis inhibitor of macrophage (AIM), also known as CD5L or Spα, is secreted by tissue macrophages. It has been reported that AIM is involved in the metabolic syndrome, which is putatively associated with the progression of chronic liver disease (CLD). In addition, we have shown that AIM is overexpressed in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) using serumproteomics. However, the association between AIM and HCV-associated CLD is not fully elucidated. Materials and Methods: 1. Serum was obtained from 6 patients with HCV-related HCC (HCC patients), 6 patients with HCV-related CLD without HCC (CLD patients), and 6 healthy volunteers. Serum proteomics was performed using 2D gel electrophoresis. 2. Serum samples were obtained from 74 HCC patients and 125 CLD patients, including 79 patients with biopsy-proved CLD. Serum levels of AIM were determined by ELISA. The homeostasis model assessmentinsulin resistance index (HOMA-IR) was calculated as fasting blood glucose × serum insulin/ 405. Results: 1. There were 27 protein spots in which the concentration in the HCC patients exceeded that of the other groups by a factor of 1.5 or more. One of these spots was identified as AIM, and differences in AIM serum levels were confirmed by ELISA. In addition, serum levels of AIM in 74 HCC patients were significantly higher than those in 125 CLD patients (4.1 vs. 1.5 μg/ml, P<0.001). 2. Serum levels of AIM were positively correlated with concentrations of type 4 collagen and negatively correlated with platelet counts, indicators of hepatic fibrosis, in all patients, and also in CLD patients without HCC. In addition, serum levels of AIM in 41 CLD patients with biopsy-proved advanced hepatic fibrosis (F2-3) were significantly higher than those in 38 patients with less-advanced hepatic fibrosis (F0-1) (1.7 vs. 1.1 μg/ml, P<0.001). Furthermore, serum levels of AIM were significantly correlated with HOMA-IR in all patients, and also in CLD patients without HCC. In contrast, these levels were not associated with hepatic steatosis or serum levels of leptin or adiponectin in biopsy-proved CLD patients. Conclusion: Our study indicated that high serum levels of AIM in patients with HCV infection are correlated with hepatic fibrosis and insulin resistance, which are possibly associated with disease progression, including HCC.