title: Lower th-1/th-2 ratio before interferon therapy may favor long-term virological responses in patients with chronic hepatitis C.
abstract: It is still controversial whether alterations in helper-T cell subpopulations contribute to the pathogenesis and clinical characteristics of chronic hepatitis C. The aim of this study was to clarify this issue, particularly in relation to interferon therapy. Thirty-one patients with histologically proven chronic hepatitis C were treated by conventional interferon (IFN) monotherapy for 6 months, and virological responses were evaluated by polymerase chain reaction 6 months later. Helper-T cell subpopulations, Th-1 and Th-2, were determined in peripheral blood by intracellular cytokine assay using flow cytometry. In chronic hepatitis C, the percentage of Th-1 and Th-2 subpopulations in peripheral blood were significantly increased, by 1.4-fold as compared with normal controls. Serum levels of ALT were inversely proportional to the percentage of Th-1 subpopulations, while directly proportional to that of Th-2 subpopulations. In nonresponders (N = 16) to interferon therapy, the percentage of Th-1 subpopulations and Th-1/Th-2 ratio were significantly higher than those in complete responders (N = 15). By multivariate logistic regression analysis, HCV genotype non-lb, HCV viral load less than 500 kilocopies/ml, and the lower Th-1/Th-2 ratio could independently merit favorable long-term virological responses. Helper-T cell subpopulations, Th-1 and Th-2, seem to contribute to progression of chronic hepatitis C in a reciprocal fashion. The imbalance between the two subpopulations may determine the final outcome of interferon therapy as one of the host factors.
authors.affiliation: Division of Gastroenterology, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Sugano
authors.initials: S
authors.lastname: Fukushima
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D012367:RNA, Viral; D016899:Interferon-beta