title: Management options for lamivudine-resistant chronic hepatitis B patients with suboptimal virological suppression by adefovir.
abstract: BACKGROUND
  In chronic hepatitis B (CHB) patients, adefovir is commonly used as a rescue therapy for lamivudine resistance, but often results in incomplete virological suppression.
  
  
  OBJECTIVE
  To study the factors predicting response to adefovir rescue, and the treatment response of tenofovir and entecavir in suboptimal responders to adefovir in CHB patients.
  
  
  METHODS
  Chronic hepatitis B patients who took adefovir for at least 6 months for lamivudine resistance were studied. Early virological response was defined as undetectable HBV DNA at month 6. Maintained virological response was defined as undetectable HBV DNA till the last follow-up.
  
  
  RESULTS
  Among 136 patients on adefovir for 39 (5-117) months, 30 (22%) had early virological response. The 3-year cumulative probability of maintained virological response was similar between patients on adefovir monotherapy (n = 53, 57.9%) and those on combination of lamivudine and adefovir treatment (n = 83, 56.5%). The month 6 HBV DNA was the only independent factor associated with maintained virological response (adjusted hazard ratio 0.49, 95% confidence interval 0.37-0.65, P < 0.001). Twenty-six of 30 (87%) early responders and 36 of 106 (34%) non-early responders had maintained virological response on adefovir (P < 0.001). Among 106 non-early responders, 18 and 11 were switched to tenofovir and entecavir, respectively. The 1-year cumulative probability of maintained virological response was higher in patients switched to tenofovir (87.5%) than those switched to entecavir (37.5%; P = 0.048) or continued with adefovir (8.7%; P < 0.001).
  
  
  CONCLUSIONS
  In adefovir rescue for lamivudine resistance, month 6 HBV DNA predicts maintained virological response in CHB patients. Switching to tenofovir achieved best viral suppression among suboptimal responders to adefovir.
authors: Institute of Digestive Disease, The Chinese University of Hong Kong; Hong Kong SAR, China.
authors: A
authors: A
authors: Ong
authors: V W-S
authors: VW
authors: Wong
authors: G L-H
authors: GL
authors: Wong
authors: H-Y
authors: HY
authors: Chan
authors: C-H
authors: CH
authors: Tse
authors: H L-Y
authors: HL
authors: Chan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives / Q000276:immunology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000276:immunology / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine