Kurashige Nao, Ohkawa Kazuyoshi, Hiramatsu Naoki, Yakushijin Takayuki, Mochizuki Kiyoshi, Oze Tsugiko, Kiso Shinichi, Kanto Tatsuya, Takehara Tetsuo, Kasahara Akinori, Doi Yoshinori, Yamada Akira, Fukuda Kazuto, Oshita Masahide, Mita Eiji, Fukui Hiroyuki, Nagase Toshihiko, Yoshihara Harumasa, Imai Yasuharu, Kato Michio, Kashihara Takeshi, Hayashi Norio
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
J Gastroenterol. 2009;44(8):864-70. doi: 10.1007/s00535-009-0076-0. Epub 2009 May 28.
A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment.
Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir. Serial changes in hepatitis B virus (HBV) DNA were correlated with the patients' baseline HBV DNA at the commencement of entecavir administration. The entecavir-resistant substitution was examined by PCR-direct sequencing. The median follow-up period of entecavir treatment was 20 (10-23) months.
All 31 patients with baseline HBV DNA <2.6 logcopies/ml maintained HBV DNA-negative status during entecavir treatment. Of seven patients having HBV DNA of 2.6-<4.0 logcopies/ml, all achieved undetectable HBV DNA at the end of follow-up. As for six patients having HBV DNA >or=4.0 logcopies/ml, three patients achieved undetectable HBV DNA, whereas virological breakthrough was observed in one patient at month 15. An entecavir-resistant virus having rtM204V, rtL180M and rtS202G substitutions was detected in this patient.
The lamivudine-to-entecavir switching treatment may be generally recommendable in CH-B patients without evidence of lamivudine resistance during the preceding lamivudine treatment. However, great care should be taken with respect to the emergence of entecavir-resistance, especially in patients who do not respond well to the preceding lamivudine treatment.
尽管换用恩替卡韦治疗可能有益，但仍有相当数量的慢性乙型肝炎（CH - B）患者持续接受拉米夫定治疗。我们调查了在先前拉米夫定治疗期间无明显拉米夫定耐药证据的CH - B患者换用恩替卡韦治疗的抗病毒疗效。
44例接受拉米夫定治疗超过6个月且无拉米夫定耐药证据的CH - B患者换用恩替卡韦。在开始恩替卡韦给药时，乙型肝炎病毒（HBV）DNA的系列变化与患者的基线HBV DNA相关。通过PCR直接测序检测恩替卡韦耐药替代突变。恩替卡韦治疗的中位随访期为20（10 - 23）个月。
所有31例基线HBV DNA<2.6 log拷贝/ml的患者在恩替卡韦治疗期间维持HBV DNA阴性状态。7例HBV DNA为2.6 - <4.0 log拷贝/ml的患者在随访结束时均实现了HBV DNA检测不到。对于6例HBV DNA≥4.0 log拷贝/ml的患者，3例实现了HBV DNA检测不到，而1例患者在第15个月出现了病毒学突破。在该患者中检测到具有rtM204V、rtL180M和rtS202G替代突变的恩替卡韦耐药病毒。
在先前拉米夫定治疗期间无拉米夫定耐药证据的CH - B患者中，拉米夫定换用恩替卡韦治疗通常可能是值得推荐的。然而，应特别注意恩替卡韦耐药的出现，尤其是对先前拉米夫定治疗反应不佳的患者。
