title: Viral response at 6 months is associated with treatment outcome of adefovir add-on therapy for lamivudine-resistance.
abstract: OBJECTIVE
  Adefovir add-on therapy is recommended for patients infected with lamivudine-resistant hepatitis B virus (HBV). We aimed to describe the long-term treatment outcome and predictors for good response of adefovir add-on therapy.
  
  
  METHODS
  A total of 559 chronic hepatitis B (CHB) patients who had been treated for at least 12 months with adefovir add-on therapy due to resistance to lamivudine were retrospectively included. Complete virologic response (CVR) was defined as serum HBV DNA <9IU/mL. Viral responses at 6months were classified as PCR negativity, partial virologic response (PVR, HBV DNA <2000 IU/mL), or inadequate virologic response (IVR, HBV DNA≥2000IU/mL).
  
  
  RESULTS
  The median duration of follow-up was 31.5 months (range, 12-56). The cumulative probabilities of CVR during adefovir add-on therapy were 58%, 70%, 78%, and 80% at 12, 24, 36, and 43 months, respectively. The cumulative rates of resistance to adefovir were 0.4%, 0.8%, and 3.1% at 12, 24, and 36 months, respectively. The only baseline factor associated with CVR (hazard ratio 0.83, 95% confidence interval 0.62-0.91, P≤0.001) and resistance to adefovir (hazard ratio 1.925, 95% confidence interval 1.13-3.30, P=0.017) was serum HBV DNA level. Comparison of the cumulative rates of CVR and resistance to adefovir according to viral response at 6months showed significant differences among the three groups (P<0.0001 and P= 0.0005, respectively).
  
  
  CONCLUSIONS
  Pre-treatment HBV DNA level and viral response at 6months is associated with treatment outcome for adefovir-add on therapy in lamivudine resistance.
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Sinn
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.forename: Joon Hyeok
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; 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; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine