A 96-week randomized trial of switching to entecavir in chronic hepatitis B patients with a partial virological response to lamivudine

作者：Heo Jeong; Park Jun Yong; Lee Heon Ju; Tak Won Young; Um Soon Ho; Kim Do Young; Yoon Ki Tae; Park Soo Young; Seo Yeon Seok; Han Kwang Hyub; Cho Mong; Ahn Sang Hoon^*

来源：Antiviral Therapy, 2012, 17(8): 1563-1570.

DOI：10.3851/IMP2277

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. %26lt;br%26gt;Methods: A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA %26gt;= 60 IU/ml after %26gt;= 6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. %26lt;br%26gt;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 entecavirswitch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P%26lt;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%26lt;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. %26lt;br%26gt;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.

• 出版日期2012