title: Evaluation of serum concentrations of human hepatocyte growth factor during interferon therapy for chronic hepatitis C.
abstract: In this study, the serum concentrations of human hepatocyte growth factor (HGF) were examined to clarify the relationship between HGF and interferon (IFN) therapy for hepatitis C. The subjects were 94 patients with chronic hepatitis C who underwent liver biopsy at our institution from 1994 through 1996. These patients were treated with natural IFN-alpha, IFNalpha(2a) and IFNalpha(2b) for periods varying from 12 to 26 weeks. Serum levels of HGF were determined in individual patients just before and after the administration of IFN and at 6 months and 1 year thereafter. The serum concentration of HGF was evaluated using enzyme-linked immunosorbent assay kits. The intra-hepatic location of HGF was explored using an immunoperoxidase-staining method. A positive correlation was found between the degree of HGF expression in the liver and the serum HGF concentrations. The degree of HGF expression in the liver decreased in the virologically sustained responders (SVRs) following IFN therapy. The serum HGF concentrations immediately after IFN therapy were lower than those before therapy in 83% of the patients. The concentrations gradually rose thereafter in about 45% of the non-responders, while it remained low or declined further in about half of the patients in this group. In the SVRs, the serum HGF concentrations declined in 88% of patients immediately after IFN therapy. Thereafter, it remained equally low or declined further in 60% of the SVRs. The serum HGF concentrations at 6 months and 1 year after IFN therapy were significantly lower in the SVRs than in the non-responders. In conclusions, serum HGF concentrations declined following IFN treatment regardless of the virological outcome of treatment. The decrease in serum HGF concentrations results from a decrease in the number of mesenchymal cells producing HGF. Consequently, evaluation of the serum HGF concentration is of clinical value for assessing changes in liver tissues after IFN therapy.
authors.affiliation: Third Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyagushi Kamimachi, Itsbashiku, Tokyo 173-8610, Japan. moriyama@med.nihon-u.ac.jp
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Moriyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumura
authors.forename: Azuma
authors.initials: A
authors.lastname: Watanabe
authors.forename: Suhu
authors.initials: S
authors.lastname: Oshiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamagami
authors.forename: Miki
authors.initials: M
authors.lastname: Kaneko
authors.forename: Atsuo
authors.initials: A
authors.lastname: Shioda
authors.forename: Naohide
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arakawa
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D017228:Hepatocyte Growth Factor / Q000097:blood* / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D007372:Interferons