title: Outcome of lamivudine-resistant chronic hepatitis B after up to 5 years of combination therapy with adefovir.
abstract: BACKGROUND
  There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B.
  
  
  METHODS
  We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe assay were determined among patients with detectable viraemia. The significance of different baseline and on-treatment virological parameters was analysed.
  
  
  RESULTS
  The median age and duration of follow-up were 45.1 years and 37.1 months, respectively. The cumulative rates of HBV DNA undetectability (<20 IU/ml), alanine aminotransferase normalization and hepatitis B e antigen seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative resistance rate to adefovir was 10.2%. Among different baseline and on-treatment virological parameters, week 24 HBV DNA<200 IU/ml was associated with an increased chance of long-term virological suppression (P<0.001, OR 13.89, 95% CI 3.90, 49.46). Primary non-response and high baseline viral titres were not useful in predicting long-term virological outcomes. The 5-year cumulative rate of serum creatinine elevation >0.5 mg/dl was 4.1%.
  
  
  CONCLUSIONS
  Combination lamivudine and adefovir therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 10.2% of patients. Week 24 HBV DNA<200 IU/ml was predictive of favourable long-term virological outcomes and could be used to assist treatment decisions on continuing lamivudine and adefovir or switching to more potent therapy.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.forename: John Chi-Hang
authors.initials: JC
authors.lastname: Yuen
authors.forename: Ivan Fan-Ngai
authors.initials: IF
authors.lastname: Hung
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology*; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D014766:Viremia / Q000821:virology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine