title: Effects of mutation number in interferon sensitivity determining region on peripheral blood CD4(+) T cell subsets (Th1, Th2) in chronic hepatitis C patients with hepatitis C virus genotype 1b and high viral load.
abstract: OBJECTIVE
  The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR.
  
  
  METHODS
  Subjects included 44 patients with CHC infected with genotype 1b and high viral load. The number of AA mutations in the ISDR was retrospectively determined using stored serum samples taken immediately before starting therapy. All patients received IFN-alpha 2b or pegylated-IFN (PEG-IFN)-alpha 2b and ribavirin. When serum hepatitis C virus-ribonucleic acid (HCV-RNA) was negative at 4 or 12 weeks after starting therapy, the patient was defined as having rapid viral response (RVR) or early viral response (EVR), respectively. CD4(+) T cell (Th1 or Th2) in peripheral blood (PB) before and until day 56 of treatment was analyzed.
  
  
  RESULTS
  Rates of RVR and EVR were 0 (0/21) and 14% (3/21), respectively, in patients with one or fewer AA mutations in the ISDR (ISDR0-1), and 30 (7/23), and 74% (17/23), respectively, with two or more AA mutations in the ISDR (ISDR > 2). Although the percentage of PB Th1 cells did not differ between the two groups during the study period, the percentage of PB Th2 cells was significantly lower in the ISDR0-1 group than in the ISDR > 2 group at baseline and on days 3, 7, 14, and 28 of treatment.
  
  
  CONCLUSIONS
  The number of AA mutations in the ISDR influenced PB Th2 cells before and until day 28, and was associated with higher RVR and EVR rates.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan. iskoji377@med.toho-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kogame
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Shiratori
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Higami
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kanayama
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Shiozawa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Wakui
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
authors.forename: Yasukiyo
authors.initials: Y
authors.lastname: Sumino