title: Impact of peginterferon alpha-2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B.
abstract: The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG-IFN) α-2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre-therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow-up period. Serum HBV DNA levels decreased by 5.2 and 3.3 log copies/ml (mean) by the end of the therapy and follow-up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4 log copies/µg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (>4.5 log copies/µg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse (P  = 0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Osaki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inuzuka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ueshima
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Inoue
authors.forename: Norihisa
authors.initials: N
authors.lastname: Yada
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004270:DNA, Circular / Q000037:antagonists & inhibitors; D004279:DNA, Viral / Q000037:antagonists & inhibitors*; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000254:growth & development; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C417083:peginterferon alfa-2b