title: Sequential therapy with adefovir dipivoxil and pegylated interferon alfa-2a for HBeAg-negative patients.
abstract: To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg-negative patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV-DNA <10 000 copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease ≥1 log(10) IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10) copies/mL and 3.8 log(10) IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log(10) IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues.
authors.affiliation: Hôpital Beaujon, Service d'Hépatologie, Clichy, France INSERM U773-CRB3, Paris, France. rami.moucari@inserm.fr
authors.forename: R
authors.initials: R
authors.lastname: Moucari
authors.forename: N
authors.initials: N
authors.lastname: Boyer
authors.forename: M-P
authors.initials: MP
authors.lastname: Ripault
authors.forename: C
authors.initials: C
authors.lastname: Castelnau
authors.forename: V
authors.initials: V
authors.lastname: Mackiewicz
authors.forename: A
authors.initials: A
authors.lastname: Dauvergne
authors.forename: D
authors.initials: D
authors.lastname: Valla
authors.forename: M
authors.initials: M
authors.lastname: Vidaud
authors.forename: M-H N
authors.initials: MH
authors.lastname: Chanoine
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D063065:Organophosphonates; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; D000225:Adenine; C100416:peginterferon alfa-2a; C106812:adefovir dipivoxil