The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV an

StephenW

PLoS One. 2012;7(3):e32789. Epub  2012 Mar 27.
The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV and Untreated with Lamivudine: A Systematic Review and Meta-Analysis.Tan Y, Ding K, Su J, Trinh X, Peng Z, Gong Y, Chen L, Cui Q, Lei N, Chen X, Yu R.
SourceDepartment of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

AbstractBACKGROUND: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B.
METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21% (95% CI: 9.69%-14.95%). China had an incidence of 13.38% (95% CI: 10.90%-16.07%) and seven other countries had an incidence of 9.90% (95% CI: 3.28%-19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients' ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C.
CONCLUSIONS: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patients untreated with lamivudine. These mutations might be the consequence of accumulated base mismatch due to the nature of viral polymerase. More fundamental and clinical studies are needed to clarify the influence of YMDD mutations in hepatitis B progression and antiviral treatment.

StephenW

PLoSOne。 2012年7（3）：e32789。 2012 EPUB 3月27日。
自然发生YMDD变异慢性感染HBV和拉米夫定未经治疗的患者之间的系统回顾和荟萃分析。
谈迎，丁钾，苏J，郑氏X，彭珍，巩远，陈力，崔Q，雷一篇友善列印，陈旭，羽河
源

流行病与卫生统计学系，公共卫生学院，南京医科大学，南京，中国。
抽象
背景：

最近的一些报告已经证明，酪氨酸（Y）的蛋氨酸（M）天门冬氨酸（D）天门冬酸（D）（YMDD变异）
可以自然发生在慢性乙型肝炎患者无拉米夫定抗病毒治疗。本文旨在评估整体的自然发病率和YMDD变异序突变，拉米夫定初治慢性乙肝病毒携带者之间的相关危险因素，从而为B型肝炎的临床治疗提供一些线索
方法/主要结果：

中文和英文文献报告未经治疗的慢性乙肝患者从2001年至2010年间的自然YMDD变异的研究进行了全面搜查。发病率估计进行了总结和分析了荟萃分析。在本次审查（13日在英国和中国的34），来自八个国家的47个符合条件的文章被选中。图案在未经治疗的慢性乙肝患者YMDD变异的突变来自八个国家的汇集发病率为12.21％（95％CI：9.69％-14.95％）。中国有13.38％的发病率（95％CI：10.90％-16.07％）和其他七个国家的发病率，分别为9.90％（95％CI：3.28％-19.55％）。拉米夫定治疗会增加突变的风险比未经治疗的患者高出5.23倍。较高的HBV DNA拷贝数与自然YMDD变异发生率增加。被发现在不同性别，年龄，HBeAg状态，病人的ALT（谷丙转氨酶）水平，HBV基因型B和C组之间的群体之间的YMDD变异发生率无显着性差异
结论：

在慢性乙型肝炎患者用拉米夫定未经处理的发病率比较高的YMDD基序的突变可发生自发性。这些突变可能是由于病毒聚合酶的性质累计碱基错配的后果。需要更多的基础与临床研究，以澄清在B型肝炎的进展和抗病毒治疗YMDD变异的影响。