title: Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B.
abstract: BACKGROUND
  Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine.
  
  
  METHODS
  HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue monotherapy for 44-48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20-24 weeks.
  
  
  RESULTS
  HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 +/-2.4 versus 7.7 +/-1.4 versus 5.1 +/-0.3 log(10) copies/ml; P=0.06), treatment and follow-up durations (45.5 +/-2.0 versus 49.7 +/-5.6 versus 48.7 +/-6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001).
  
  
  CONCLUSIONS
  Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.
authors.affiliation: Liver Unit, Cathay General Hospital Medical Center, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hatakeyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Jui-Ting
authors.initials: JT
authors.lastname: Hu
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Sien-Sing
authors.initials: SS
authors.lastname: Yang
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000494:pharmacology*; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D007372:Interferons