title: Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance.
abstract: This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25-69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3-8.0) log(10) copies/mL, and the median duration of ETV therapy was 24 (12-47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387-7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P < 0.001) but also lower probability of experiencing a virologic breakthrough (P = 0.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow-up period. Cumulative breakthrough rates at 6, 12, 24 and 36 months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV-refractory CHB patients with prior LMV resistance.
authors.affiliation: Department of Internal Medicine, Hallym University Medical Center, Seoul, Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: D D
authors.initials: DD
authors.lastname: Seo
authors.forename: J S
authors.initials: JS
authors.lastname: Jang
authors.forename: W G
authors.initials: WG
authors.lastname: Shin
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: M K
authors.initials: MK
authors.lastname: Jang
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: H Y
authors.initials: HY
authors.lastname: Kim
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: C K
authors.initials: CK
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine