title: Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study.
abstract: A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in subjects with chronic hepatitis B who had hepatic decompensation (Child-Turcotte-Pugh score ≥7). Adult subjects were randomized and treated (n = 191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were positive or negative for hepatitis B e antigen and experienced or naive for treatment with nucleos(t)ide analogues. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA, as determined by polymerase chain reaction, at week 24, adjusted for baseline HBV DNA and lamivudine resistance status by linear regression analysis. Entecavir demonstrated superiority to adefovir for this endpoint (treatment difference 1.74 log(10) copies/mL [95% confidence interval -2.30, -1.18]; P < 0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all time points through week 48 and a higher proportion of subjects who achieved HBV DNA < 300 copies/mL at weeks 24 (entecavir 49%; adefovir 16%; P < 0.0001) and 48 (entecavir 57%; adefovir 20%; P < 0.0001). Approximately two-thirds of subjects in both groups showed improvement/stabilization in Child-Turcotte-Pugh status. Model for End-Stage Liver Disease score change at week 48 was -2.6 for entecavir and -1.7 for adefovir. Adverse event rates were comparable between groups. Cumulative hepatocellular carcinoma rates were 12% for entecavir and 20% for adefovir. Cumulative death rates were 23% for entecavir and 33% for adefovir. Week 24 mortality rates were 12% for both groups. conclusion: Entecavir demonstrated superior virologic efficacy to adefovir in a population of patients with chronic hepatitis B who had hepatic decompensation. Biochemical and clinical benefits were also demonstrated. Entecavir was well tolerated, and early mortality rates were consistent with rates observed in similar populations treated with lamivudine.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. liveryfl@gmail.com
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.forename: Maria
authors.initials: M
authors.lastname: Raptopoulou-Gigi
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Sarin
authors.forename: Tawesak
authors.initials: T
authors.lastname: Tanwandee
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Lennox
authors.initials: L
authors.lastname: Jeffers
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
authors.forename: Jolanta
authors.initials: J
authors.lastname: Bialkowska
authors.forename: Shijie
authors.initials: S
authors.lastname: Tang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Beebe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cooney
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D017093:Liver Failure / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine