title: A 96-week randomized trial of switching to entecavir in chronic hepatitis B patients with a partial virological response to lamivudine.
abstract: BACKGROUND
  Growing numbers of chronic hepatitis B (CHB) patients in the Asia-Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96-week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virological response to lamivudine.
  
  
  METHODS
  A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA≥60 IU/ml after ≥6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day.
  
  
  RESULTS
  Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/ml, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P<0.001). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by week 4, maintained through week 96. Entecavir-switch patients with baseline HBV DNA<5 log(10) IU/ml were more likely to achieve a virological response at week 96. A total of 6 (17.6%) entecavir-switch and 2 (5.7%) lamivudine-maintained patients achieved HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks.
  
  
  CONCLUSIONS
  Switching to entecavir in patients with a partial virological response to lamivudine resulted in increased virological efficacy and lower rates of antiviral resistance than maintaining lamivudine.
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Heon Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Yoon
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Mong
authors.initials: M
authors.lastname: Cho
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D057915:Drug Substitution; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; C413685:entecavir; D006147:Guanine