Emergence of multidrug resistance in patients with chronic hepatitis B treated by combination therapy with adefovir plus lamivudine or entecavir monotherapy and efficacy of tenofovir therapy.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590999
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Okinaka Memorial Institute for Medical Research
• Principal Investigator: SUZUKI Fumitaka 公益財団法人冲中記念成人病研究所, その他部局等, 研究員 (80322642)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Ｂ型肝炎 / ラミブジン / アデホビル / エンテカビル / テノホビル / 多剤耐性ウイルス / 次世代シークエンサー

Outline of Final Research Achievements

We analyzed 406 Japanese patients with lamivudine-refractory chronic hepatitis B treated with lamivudine plus adefovir dipivoxil combination therapy. Substitutions associated with multidrug resistance were identified in 11 patients (2.7%) at baseline, and in 12 patients (3%) during lamivudine plus adefovir dipivoxil therapy. Moreover, we analyzed naïve 976 patients treated entecavir monotherapy. Substitutions associated with entecavir resistance were identified in 9 patients (1%) during entecavir monotherapy. Moreover, these 44 patients with multidrug resistance received tenofovir disoproxil fumarate (TDF) therapy. Ratio of patients with undetectable serum HBV DNA levels during TDF therapy was 67% and 87% at years 1 and 2, respectively. However, viral breakthrough occurred in 2 patients during TDF therapy. Where indicated, HBV DNA and virological analysis should be carefully monitored.

Free Research Field

肝臓内科