title: Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation.
abstract: It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At＞3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Tsuzaki
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koike
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Susumu
authors.initials: S
authors.lastname: Shinoura
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Umeda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yoshida
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nobuoka
authors.forename: Masashi
authors.initials: M
authors.lastname: Utsumi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000276:immunology / Q000601:surgery*; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda