Matsuda Marie, Suzuki Fumitaka, Suzuki Yoshiyuki, Tsubota Akihito, Akuta Norio, Hosaka Tetsuya, Someya Takashi, Kobayashi Masahiro, Saitoh Satoshi, Arase Yasuji, Satoh Junko, Takagi Kimiko, Kobayashi Mariko, Ikeda Kenji, Kumada Hiromitsu
Research Institute for Hepatology, Toranomon Branch Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki 213-8587, Japan.
J Gastroenterol. 2004 Jan;39(1):34-40. doi: 10.1007/s00535-003-1242-4.
Lamivudine is used for the treatment of chronic hepatitis B (CH-B), and exhibits excellent antiviral activity. However, longterm administration increases the likelihood of the emergence of resistant viruses, with an accompanying relapse of hepatitis. However, recent studies have reported lamivudine-resistant viruses in patients with CH-B before such treatment. The aim of this study was to investigate whether YMDD mutants occur in nature.
The existence of lamivudine-resistant viruses was examined in 20 asymptomatic carriers of hepatitis B virus (ASC), 10 patients who lost hepatitis B surface antigen (HBsAg) during follow-up and in 20 lamivudine-treated patients with and without breakthrough hepatitis. Both polymerase chain reaction (PCR) restriction fragment length polymorphism and SMITEST hepatitis B virus (HBV)-YMDD mutation detection methods were used to detect resistant viruses.
No YMDD mutants were detected in the sera of the 20 ASC at the initial and final medical examinations, nor were YMDD mutants detected in sera collected at the initial medical examination, about 6 months before, or immediately after the loss of HBsAg in the 10 patients. In the 20 patients treated with lamivudine, YMDD mutants were not detected in any of them before treatment, whereas mutants were detected in the sera of 10 patients during treatment.
Our results suggest that lamivudine-resistant YMDD mutant viruses were present in a few patients with HBV infection before they have been treated with lamivudine.
拉米夫定用于治疗慢性乙型肝炎（CH - B），具有出色的抗病毒活性。然而，长期使用会增加耐药病毒出现的可能性，并伴随肝炎复发。不过，近期研究报道了在接受此类治疗前的CH - B患者中存在拉米夫定耐药病毒。本研究的目的是调查YMDD突变体是否在自然状态下存在。
对20名无症状乙型肝炎病毒携带者（ASC）、10名在随访期间失去乙肝表面抗原（HBsAg）的患者以及20名接受拉米夫定治疗且有或无突破性肝炎的患者检测拉米夫定耐药病毒的存在情况。采用聚合酶链反应（PCR）限制性片段长度多态性和SMITEST乙肝病毒（HBV）-YMDD突变检测方法检测耐药病毒。
在20名ASC的初次和末次体检血清中均未检测到YMDD突变体，在10名患者初次体检时、HBsAg消失前约6个月或消失后立即采集的血清中也未检测到YMDD突变体。在20名接受拉米夫定治疗的患者中，治疗前均未检测到YMDD突变体，而治疗期间在10名患者的血清中检测到了突变体。
我们的结果表明，在一些乙肝病毒感染患者接受拉米夫定治疗之前就存在拉米夫定耐药的YMDD突变病毒。
