Comparative serum proteomic analysis of patients with acute-on-chronic liver failure: alpha-1-acid glycoprotein maybe a candidate marker for prognosis of hepatitis B virus infection

Abstract

The acute-on-chronic liver failure (AoCLF) caused by hepatitis B virus (HBV) infection remains to be a challenge in clinics with a high mortality rate in China, and it is important to identify biomarkers to foresee the prognosis of patients with HBV. The current study analysed serum proteome changes of acute-on-chronic liver failure as a result of acute exacerbation of chronic hepatitis B infection. Serum samples were collected from normal subjects (NS, n = 8), patients with chronic hepatitis B (CHB, n = 12) and patients with AoCLF (n = 12). After removal of albumin/IgG and ultramembrane centrifugation, serum proteins were separated by two-dimensional gel electrophoresis. Differentially expressed spots were identified by matrix-associated laser desorption ionization time-of-flight tandem mass spectrometry. Through the removal of albumin/IgG and ultramembrane centrifugation, the well-resolved and reproducible two-dimensional gel electrophoresis (2-DE) profiles were obtained. A total of 23 proteins were identified on 2-DE profiles by their differential expression between the three cohorts. Mass spectrometry analysis resulted in the identification of 12 proteins unambiguously. Western blot analysis confirmed the proteomics results that the α1-acid glycoprotein (α1-AGP) levels decrease significantly in plasma of patients with AoCLF, but somewhat decreased in patients with chronic HBV. Further α1-AGP levels in bulk serum samples were measured by immune turbidimetry including normal subjects group (n = 25), acute hepatitis group (n = 36), chronic hepatitis group (n = 52) and AoCLF group (n = 48), the level of α1-AGP in AoCLF groups sharply decrease than other groups. Our study shows that α1-AGP may be a potential plasma biomarker for AoCLF diagnosis because of acute exacerbation of chronic hepatitis B infection.