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中国南方地区乙型肝炎病毒拉米夫定耐药突变的分子流行特征。

Molecular epidemical characteristics of Lamivudine resistance mutations of HBV in southern China.

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Sichuan Province, China.

出版信息

Med Sci Monit. 2011 Oct;17(10):PH75-80. doi: 10.12659/msm.881965.

Abstract

BACKGROUND

Lamivudine (LMV), as the preferred oral drug for use in treatment of HBV, always results in development of resistance mutations after long-term treatment. In this study we investigated chronic hepatitis B (CHB) patients in southern China to determine whether different HBV genotypes affect the incidence of LMV resistance mutations.

MATERIAL/METHODS: The study recruited 185 CHB patients living in southern China. Enzyme-linked immunosorbent assay was used to test for HBV serological markers, and HBV DNA was quantified by real-time PCR. Sequencing was performed to detect HBV genotypes and mutations.

RESULTS

There were 49.19% (91/185) CHB patients with HBV resistant to LMV. Only 2 genotypes were found: B and C; 62.16% (115/185) of patients were infected with genotype B HBV and 37.84% (70/185) of patients were infected with genotype C HBV. The incidence rate of LMV resistance was not significantly different between genotype B and C (49.57% vs. 48.57%, P>0.05). For the mean age and sex ratio, no significant difference was found. The pattern of rtM204I alone was predominantly observed (36.26%, 33/91), followed by rtM204V+rtL180M (23.08%, 21/91). The overall incidence rate of rtM204I mutation in genotype B (45.61%, 26/57) was more frequent than that in genotype C (20.59%, 7/34) (45.61% vs. 20.59%, P<0.05), but the incidence rate of other mutation patterns was not significantly different between genotypes B and C.

CONCLUSIONS

Our results emphasize that a LMV resistance test before treatment is of great importance in rational and optimal CHB therapy.

摘要

背景

拉米夫定(LMV)作为治疗乙型肝炎病毒(HBV)的首选口服药物,长期治疗后总会导致耐药突变的产生。本研究旨在调查中国南方的慢性乙型肝炎(CHB)患者,以确定不同的 HBV 基因型是否会影响 LMV 耐药突变的发生率。

材料/方法:本研究招募了 185 名居住在中国南方的 CHB 患者。采用酶联免疫吸附试验检测 HBV 血清学标志物,实时 PCR 定量检测 HBV DNA。测序用于检测 HBV 基因型和突变。

结果

有 49.19%(91/185)的 CHB 患者对 LMV 耐药。仅发现 2 种基因型:B 和 C;62.16%(115/185)的患者感染 B 型 HBV,37.84%(70/185)的患者感染 C 型 HBV。B 型和 C 型 LMV 耐药的发生率无显著差异(49.57%比 48.57%,P>0.05)。在平均年龄和性别比例方面,无显著差异。主要观察到 rtM204I 单一突变模式(36.26%,33/91),其次是 rtM204V+rtL180M(23.08%,21/91)。B 型基因型中 rtM204I 突变的总发生率(45.61%,26/57)高于 C 型基因型(20.59%,7/34)(45.61%比 20.59%,P<0.05),但 B 型和 C 型基因型之间其他突变模式的发生率无显著差异。

结论

我们的研究结果强调,在合理和优化的 CHB 治疗之前,进行 LMV 耐药检测非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd3/3539467/8e440f0be646/medscimonit-17-10-PH75-g001.jpg

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