title: Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B.
abstract: OBJECTIVE
  The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment.
  
  
  METHODS
  Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks.
  
  
  RESULTS
  The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log(10) IU/mL, week 96: -4.27 log(10) IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm.
  
  
  CONCLUSIONS
  There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Mi Sung
authors.initials: MS
authors.lastname: Park
authors.forename: Beom Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Ja Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Seung Up
authors.initials: SU
authors.lastname: Kim
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Oidov
authors.initials: O
authors.lastname: Baartarkhuu
authors.forename: Kwang Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Adefovir; Entecavir; Hepatitis B; Hepatitis B virus; Multidrug resistance