A 96-week randomized trial of switching to entecavir in patients who achieved virological suppression on lamivudine therapy

作者：Ahn Sang Hoon; Heo Jeong^*; Park Jun Yong; Woo Hyun Young; Lee Heon Ju; Tak Won Young; Um Soon Ho; Yoon Ki Tae; Park Soo Young; Kim Chang Wook; Kim Hyung Hoi; Han Kwang Hyub; Cho Mong

来源：Journal of Gastroenterology and Hepatology, 2016, 31(4): 865-871.

DOI：10.1111/jgh.13231

• entecavir
• hepatitis B
• lamivudine

Background and Aim:There are limited data assessing whether patients who achieved virological suppression on lamivudine but remain hepatitis B e antigen-positive should be switched to a more potent antiviral with a high genetic barrier to resistance or continue with lamivudine. We compared the safety and efficacy of switching with entecavir versus continuing lamivudine.
Methods:This was a Phase IV, randomized, open-label, prospective study in a tertiary care setting. Seventy-three chronic hepatitis B patients who achieved virological suppression on lamivudine (serum hepatitis B virus DNA<60International Unit (IU)/mL) were enrolled. Entecavir or lamivudine were administered orally for up to 96weeks. Virologic and serologic responses were measured throughout the study.
Results:A significantly higher proportion of patients in the entecavir group achieved hepatitis B virus DNA<60IU/mL at Weeks 48 (100% [38/38] vs 62.8% [22/35]; P<0.001) and 96 (97.4% [37/38] vs 57.1% [20/35]; P<0.001). A greater number of patients had virologic breakthrough (Week 96 cumulative incidence 42.9% vs 2.6%; P<0.001) and genotypic lamivudine resistance (28.6% [10/35] vs 0% [0/38]; P<0.001) in the lamivudine group. No serious adverse events or laboratory abnormalities were reported.
Conclusions:Even after achieving virological suppression on lamivudine therapy, the risk of emergent lamivudine resistance increases over time. Switching to entecavir resulted in a maintained virologic response and superior serologic responses versus continued lamivudine therapy. This study supports a rationale for switching to entecavir in chronic hepatitis B patients with virological suppression on lamivudine.

• 出版日期2016-4