Lamivudine resistance - 2 abstracts

StephenW

World J Gastroenterol. 2011 Dec 7;17(45):4987-92.
Lamivudine resistance mutations in patients infected with hepatitis B virus
genotype D.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22174548
Yildiz O, Aygen B, Demirtürk N, Demirdal T, Inan D, Yildirmak T, Kantürk
A, Tütüncü E, Group HB. SourceOrhan Yildiz, Bilgehan Aygen, Department
of Infectious Diseases and Clinical Microbiology, Medical School of Erciyes
University, 38039 Kayseri, Turkey.

Abstract
AIM: To determine the distribution of viral genotypes for primary or
acquired lamivudine resistance.

METHODS: A total of 283 patients with chronic hepatitis B virus (HBV)
infection (245 patients with chronic hepatitis B and 38 inactive hepatitis
B surface antigen carriers) were included in the study. The HBV genotype
was determined by using quantitative real-time polymerase chain reaction
and sequence analysis, and tyrosine-methionine-aspartate-aspartate (YMDD)
motif mutations were determined using the reverse transcriptase
hybridization method.

RESULTS: Lamivudine resistance was determined in a total of 25 (10.7%)
chronic hepatitis B patients. Eight subjects (4%) had primary resistance to
lamivudine, and 17 (53.1%) had secondary resistance to lamivudine. Genotype
D, which was isolated from 267 of the patients with chronic HBV infection,
was the dominant genotype in Turkey.

CONCLUSION: Identification of YMDD motif mutations should have a positive
impact on the selection of proper antiviral medication for patients, even
for those who are nucleoside naïve.




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StephenW

世界胃肠病学杂志。 2011年12月7日;17（45）:4987- 92。
在与乙肝病毒感染的患者拉米夫定耐药突变
D基因型来源：http://www.ncbi.nlm.nih.gov/pubmed/22174548
Yildiz澳，Aygen乙，Demirtürkñ，Demirdal INANð，Yildirmak T，Kantürk
一，Tütüncü E，集团HB。 SourceOrhan Yildiz，Bilgehan Aygen，处
传染病和埃尔吉耶斯医学院临床微生物学，
大学，38039土耳其开塞利，。

摘要
目的：确定为小学或病毒基因型的分布
获得拉米夫定耐药性。

方法：共有283例慢性乙型肝炎病毒（HBV）
感染（245例慢性乙型肝炎患者和38名非活动性肝炎
乙肝表面抗原携带者）被列入了研究。 HBV基因型
由采用实时定量聚合酶链反应
和序列分析，与酪氨酸 - 蛋氨酸 - 天门冬氨酸，天门冬氨酸（YMDD）
图案突变的确定，采用逆转录
杂交方法。

结果：拉米夫定耐药性测定中共有25例（10.7％）
慢性乙型肝炎患者。 8个科目（4％）原发耐药
拉米夫定，和17（53.1％）继发性耐药拉米夫定。基因型
D，这是由慢性乙肝病毒感染的患者267隔离，
在土耳其的优势基因型。

结论：YMDD基序突变的鉴定应该有一个积极的
为患者选择适当的抗病毒药物的影响，甚至
对于那些核苷天真。

StephenW

J Med Virol. 2012 Feb;84(2):217-22. doi: 10.1002/jmv.23191.
Pre-existing YMDD mutants in treatment-naïve patients with chronic
hepatitis B are not selected during lamivudine therapy.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22170540
Lee SH, Kim HS, Byun IS, Jeong
SW, Kim SG, Jang JY, Kim YS, Kim BS. SourceDepartment of Internal Medicine,
Soonchunhyang University College of Medicine, Cheonan, Korea.

Abstract
Although the rate at which mutations in the
tyrosine-methionine-aspartate-aspartate (YMDD) motif of hepatitis B virus
polymerase form is high during prolonged lamivudine (LAM) therapy, these
mutations sometimes occur naturally in treatment-naïve patients with
chronic hepatitis B. The prevalence of natural YMDD mutants differs
geographically, and its clinical significance during LAM therapy is
unknown. This study aimed to investigate whether pre-existing YMDD mutants
were selected during LAM therapy. It included 14 treatment-naïve patients
who were treated with LAM for at least 9 months. LAM resistance was
evaluated before and at 3-month intervals during treatment. Mutations were
analyzed by direct sequencing, restriction fragment mass polymorphism
(RFMP) assays, and a single-step multiplex polymerase chain reaction (PCR)
test using dual-priming oligonucleotide (DPO) primers. DPO-based multiplex
PCR showed two YMDD mutations in two patients before LAM therapy; rtM204V
and rtL180M?+?rtM204V/I. Further, two patients had an rtL180M mutation
without an accompanying rtM204V/I mutation. No mutant was detected in any
patient by direct sequencing or the RFMP assay before LAM therapy. A
virological response was observed at 3 months in all patients with
pre-existing YMDD mutants. All mutations disappeared after 3 months of LAM
therapy, and during the follow-up period, no re-emergence was detected by
any of the three methods. Further, the viral load was suppressed optimally.
In conclusion, pre-existing YMDD mutants were cleared early during the
course of LAM therapy, which produced a consistent virological response,
and the mutants were not selected by LAM therapy. J. Med. Virol.
84:217-222, 2012. © 2011 Wiley Periodicals, Inc.

StephenW

数字医学Virol 2012年2月84（2）:217 - 22。作者：10.1002/jmv.23191。
在治疗慢性乙型肝炎的初治患者的预现有的YMDD突变
在拉米夫定治疗乙肝没有选中。来源：
http://www.ncbi.nlm.nih.gov/pubmed/22170540李SH，金协，卞，郑某
西南，金兴，张集旸，金渝生，金BS。 SourceDepartment的内科，
顺天乡大学医学院，韩国天安。

摘要
虽然利率在突变
乙型肝炎病毒酪氨酸 - 蛋氨酸 - 天门冬氨酸，天门冬氨酸（YMDD）基序
聚合酶形成高，在长时间的拉米夫定（LAM）治疗，这些
突变，有时会发生在治疗过的病人，自然
慢性乙型肝炎自然YMDD突变的发生率不同
地理，和林治疗期间的临床意义
未知之数。本研究旨在探讨是否预先存在的YMDD突变
被选定在林治疗。它包括14个治疗过的病人
与林治疗至少9个月。林耐
评估前和治疗期间每隔3个月。突变
通过直接测序，限制性片段质谱多态性分析
（RFMP）检测，单步多重聚合酶链反应（PCR）
测试使用双吸寡核苷酸（DPO）的引物。 DPO的，基于复
PCR结果显示前两林治疗的患者YMDD变异; rtM204V
和rtL180M + rtM204V / I。此外，两名病人有rtL180M突变
不附带rtM204V / I突变。没有发现任何突变
直接测序或RFMP检测前林治疗的患者。一
在3个月所有患者的观察与病毒学应答
预先存在的YMDD突变。所有突变后消失3个月的林
治疗，并在后续期间，没有再出现检测
任何的三种方法。此外，病毒载量是最佳的抑制。
总之，预先存在的YMDD突变早在清除
当然，林治疗，这就产生了一致的病毒学应答，
和突变林治疗选择。 J.医学。 Virol。
84:217-222，2012年。 © 2011威利期刊公司