Mass spectrometry-based plasma peptide profiling of acute exacerbation in HBeAg-positive chronic hepatitis B.

BACKGROUND: Acute exacerbations (AE) of serum alanine aminotransferase activities that are 5 times above the normal upper limit frequently occur during the immune clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB). It is unclear how the varying clinical severities of AE reflect differences in the underlying immune responses against the hepatitis B virus. METHODS: We utilized magnetic bead-based purification methods coupled with MALDI-TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB patients experiencing AE without and with clinical decompensation. RESULTS: Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory spectral profile than immobilized Cu(2+) metal ion affinity chromatography did for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support Vector Machine, a classification model consisting of 5 classifiers was determined to give a sensitivity of 94.7% and a specificity of 75% for differentiating patients with and without decompensation. Classifiers identified as fragments derived from transthyretin and apolipoprotein A-IV were significantly decreased and increased in patients with decompensation, respectively. CONCLUSIONS: Our study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass spectrometry can be used for differentiating AE with and without decompensation in patients with HBeAg-positive CHB.

Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. METHODS: MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. RESULTS: A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. CONCLUSIONS: Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.