title: Factors associated with the effect of interferon-α sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B.
abstract: OBJECTIVE
  The factors associated with the outcome of sequential therapy with interferon-α (IFN-α) in order to halt nucleoside/nucleotide analog (NUC) maintenance treatment for chronic hepatitis B were analyzed.
  
  
  METHODS
  A total of 50 patients with chronic hepatitis B who underwent IFN-α sequential therapy for cessation of NUC were enrolled retrospectively. The subjects received NUC plus IFN-α for 4 weeks followed by IFN-α alone for 20 weeks. Natural IFN-α of 6-MU doses was administrated three times a week. A successful response to NUC/IFN-α sequential therapy was defined as serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL, serum alanine aminotransferase (ALT) below 30 IU/L, and hepatitis B e-antigen negativity at 24 months after completing the treatment.
  
  
  RESULTS
  Multivariate analysis revealed that hepatitis B surface antigen (HBsAg) of 3.0 log U/mL or more (P < 0.002) and hepatitis B core-related antigen (hepatitis B core-related antigen [HBcrAg]) of 4.5 log U/mL or more (P < 0.003) at the start of IFN-α administration were significant factors associated with a 24-month non-response. Maximal levels of ALT and HBV DNA during the follow-up period after completing IFN-α therapy were significantly related (P < 0.001), and receiver operating characteristic analysis showed that both maximal ALT (P < 0.001) and HBV DNA (P < 0.001) were significantly related to the final 24-month response.
  
  
  CONCLUSIONS
  The combinational use of HBsAg and HBcrAg levels may be useful to predict the 24-month outcome of NUC/IFN-α sequential therapy. Maximal levels of ALT and HBV DNA during post-treatment follow-up may also help monitor responses to IFN-α sequential therapy.
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima.
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.affiliation: Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya.
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto.
authors.forename: Shiho
authors.initials: S
authors.lastname: Miyase
authors.affiliation: Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo.
authors.forename: Jong-Hon
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Shinkai
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto.
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
keywords: hepatitis B core-related antigen; hepatitis B surface antigen; interferon-α; nucleoside/nucleotide analogs; sequential therapy