title: Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine: a 5-year study of patients with hepatitis B with lamivudine resistance.
abstract: To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.0-8.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P = 0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R = -0.38, P = 0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV.
authors.affiliation: Dentistry and Pharmaceutical Sciences, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Okayama, Japan. fikeda@md.okayama-u.ac.jp
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Baba
authors.forename: Koichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kubota
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fujioka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritou
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kobashi
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil