title: Efficacy of adefovir add-on lamivudine rescue therapy compared with switching to entecavir monotherapy in patients with lamivudine-resistant chronic hepatitis B.
abstract: No study has reported on the comparative effect of adefovir (ADV) add-on lamivudine (LAM) versus switching to entecavir (ETV) in LAM-resistant patients with chronic hepatitis B. From October 2007 to September 2008, 92 consecutive LAM-resistant patients were enrolled (47 LAM+ADV and 45 ETV 1 mg). All patients were followed for at least 12 months. The parameters assessed included normalization of ALT, HBeAg seroconversion, undetectable HBV DNA, reduction of HBV DNA, and predictors of virologic response. In the LAM+ADV and ETV groups, the baseline DNA levels were 7.61 (5.19-9.49) and 7.10 (5.43-9.74)log(10)copies/ml, respectively. At month 12, a virologic response occurred in 18/47 (38.3%) and 11/45 (24.4%; P=0.182) patients; ALT normalization, in 39/41 (95.1%) and 36/40 (90.0%; P=0.432); HBeAg seroconversion, in 5.1% and 2.4% (P=0.606); and virologic breakthrough, in 2.1% and 11.1% (P=0.107), respectively. The mean reduction from the baseline HBV DNA level was greater in the LAM+ADV group at month 12 (3.80 ± 1.12 vs. 2.7 ± 1.32 log(10)copies/ml; P<0.001). In the multivariate analysis, the independent parameters related to a virologic response at month 12 were baseline ALT (OR=1.003, 95% CI=1.000-1.006, P=0.026) and baseline HBV DNA (OR=0.495, 95% CI=0.298-0.823, P=0.007). Compared with switching to ETV monotherapy, ADV add-on LAM therapy was more effective at reducing the viral load in patients with LAM resistance, and the baseline HBV DNA and ALT levels were independent predictors of the virologic response. However, ADV add-on therapy had limitations in patients with a higher baseline HBV DNA in LAM rescue therapy.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Han Jak
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Myoung Ha
authors.initials: MH
authors.lastname: Lee
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine