title: Difference in serum complement component C4a levels between hepatitis             C virus carriers with persistently normal alanine aminotransferase levels or chronic             hepatitis C.
abstract: Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (≤ 30 IU/l) accompanied by normal platelet counts (≥ 15 x 10(4)/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.
authors.affiliation: Digestive and Lifestyle Diseases, Department of Human and Environmental                     Sciences, Kagoshima University Graduate School of Medical and Dental Sciences,                     Kagoshima, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Imakiire
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Fumisato
authors.initials: F
authors.lastname: Sasaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mawatari
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Sherri O
authors.initials: SO
authors.lastname: Stuver
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D002353:Carrier State / Q000097:blood / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D015934:Complement C4a / Q000032:analysis*; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity*; D018936:Hepatitis C Antigens / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D040901:Proteomics; D012367:RNA, Viral / Q000235:genetics; D012698:Serologic Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014758:Viral Core Proteins / Q000097:blood
chemical_list: D015415:Biomarkers; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D015934:Complement C4a; D000410:Alanine Transaminase