Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C

Imakiire,Kazuyuki; Uto,Hirofumi; Sato,Yuko; Sasaki,Fumisato; Mawatari,Seiichi; Ido,Akio; Shimoda,Kazuya; Hayashi,Katsuhiro; Stuver,Sherri  O.; Ito,Yoshito; Okanoue,Takeshi; Tsubouchi,Hirohito

doi:10.3892/mmr.2012.924

Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C

Authors:
- Kazuyuki Imakiire
- Hirofumi Uto
- Yuko Sato
- Fumisato Sasaki
- Seiichi Mawatari
- Akio Ido
- Kazuya Shimoda
- Katsuhiro Hayashi
- Sherri O. Stuver
- Yoshito Ito
- Takeshi Okanoue
- Hirohito Tsubouchi
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Affiliations: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan , Miyazaki Prefectual Industrial Support Foundation, Miyazaki, Japan, Division of Gastroenterology and Hematology, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan, Center for Medical Education, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan, Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA, Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan , Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
Published online on: May 21, 2012 https://doi.org/10.3892/mmr.2012.924
Pages: 259-264
Copyright: © Imakiire et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (≤30 IU/l) accompanied by normal platelet counts (≥15x104/µl); these individuals show milder disease activity and slower progression to cirrhosis. This study aimed to elucidate the characteristics of HCV carriers with PNALT using serum proteomics. The first group of subjects, who underwent clinical evaluation in the hospital, consisted of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1) patients. The second group of subjects was part of a cohort study on the natural history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2) patients. Affinity bead-purified serum protein was subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Serum proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from 1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among these peaks, a 1738‑m/z peak protein was identified as a fragment of complement component 4 (C4) and correlated significantly with serum C4a concentrations as determined by enzyme immunoassay. Serum C4a levels were also significantly higher in the PNALT-2 group compared to the CHC-2 group and healthy volunteers. Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with transaminase levels, but not with other biochemical tests, HCV core antigen levels, peripheral blood cell counts or serum hepatic fibrosis markers. This study indicates that host factors such as C4a not only differ between HCV carriers with PNALT and CHC, but that proteomic approaches could also contribute to the elucidation of factors in PNALT as more differences are discovered.

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