Gervain Judit, Papp Istvánné, Csöndes Mihály, Nemesánszky Elemér, Rácz István, Ribiczey Pál, Telegdy László, Tornai István, Weisz György
Fejér Megyei Szent György Kórház, I. Belgyógyászat, Hepato-Pancreatologiai Részleg és Vírusszerológiai Laboratórium, Székesfehérvár.
Orv Hetil. 2003 Jun 22;144(25):1251-6.
In addition to interferon, lamivudine is the other widely used antiviral agent in the therapy of chronic hepatitis B. This nucleoside analogue inhibits the RNA-dependent DNA polimerase and the reverse transcription by integrating in the viral DNA, which results in the secondary suppression of viral protein synthesis and replication of HBV. It has numerous advantages such as effective viral inhibition, mild side effects and the possibility of oral administration; on the other hand it poses the problem of time-correlated appearance of lamivudine resistant mutants during therapy.
In the Virusserology Laboratory of the Department I. Internal Medicine, Szent György Hospital, Székesfehérvár, detection and type determination of the therapy resistant mutants in the C and B domains of HBV DNA polimerase gene has been carried out the for one year. In this paper, the authors review the molecular biological background of lamivudine resistance and summarise the applied test methodologies and the early results.
Six-month and/or 12-, 18-month samples of 18 chronic hepatitis B patients (4 women/14 men) treated in seven Hepatology Centres in Hungary were analysed.
Mutants of codons 528, 552, and 555 in the HBV polimerase gene were determined by nested polimerase chain reaction and reverse hybridisation.
M528, V552, I552 and I555 mutants in different variations could be detected in ten out of 18 patients.
Nowadays, drug therapy is the only treatment option used for the therapy of early and progressed chronic hepatitis B in Hungary. This new diagnostic technique was introduced to clarify the background of ineffective lamivudine therapy. Therapy resistance can occur due to the lack of reaction or the appearance of the special, therapy resistant mutants of the virus. Detection of these YMDD mutants together with the clinical picture and the biochemical and virological parameters can help in forming a decision about cessation of lamivudine therapy or application of a new drug.
除干扰素外，拉米夫定是治疗慢性乙型肝炎时另一种广泛使用的抗病毒药物。这种核苷类似物通过整合到病毒DNA中抑制RNA依赖性DNA聚合酶和逆转录，从而导致病毒蛋白合成和乙肝病毒复制的继发性抑制。它具有许多优点，如有效的病毒抑制、轻微的副作用以及口服给药的可能性；另一方面，它带来了治疗期间与时间相关的拉米夫定耐药突变体出现的问题。
在塞克什白堡圣乔治医院第一内科病毒血清学实验室，对乙肝病毒DNA聚合酶基因C和B结构域中的治疗耐药突变体进行了为期一年的检测和类型确定。在本文中，作者回顾了拉米夫定耐药的分子生物学背景，并总结了应用的检测方法和早期结果。
分析了匈牙利七个肝病中心治疗的18例慢性乙型肝炎患者（4名女性/14名男性）的6个月和/或12个月、18个月的样本。
通过巢式聚合酶链反应和反向杂交确定乙肝病毒聚合酶基因中528、552和555密码子的突变体。
18例患者中有10例检测到不同变异的M528、V552、I552和I555突变体。
目前，药物治疗是匈牙利早期和进展期慢性乙型肝炎治疗的唯一选择。引入这项新的诊断技术以阐明拉米夫定治疗无效的背景。治疗耐药可能是由于缺乏反应或病毒出现特殊的、治疗耐药突变体。检测这些YMDD突变体以及临床症状、生化和病毒学参数有助于决定是否停止拉米夫定治疗或应用新药。
