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伊朗西南部阿瓦士市未经治疗的慢性乙肝病毒感染患者中乙肝病毒逆转录酶区域的突变分析

Mutation analysis of hepatitis B virus reverse transcriptase region among untreated chronically infected patients in Ahvaz city (South-West of Iran).

作者信息

Hamidi-Fard M, Makvandi M, Samarbaf-Zadeh A, Hajiani E, Shayesteh A, Masjedizadeh A

机构信息

Infectious and Tropical Diseases Research Center , Ahvaz Jundishapur University of medical sciences, Ahvaz, Iran.

出版信息

Indian J Med Microbiol. 2013 Oct-Dec;31(4):360-5. doi: 10.4103/0255-0857.118882.

DOI:10.4103/0255-0857.118882
PMID:24064642
Abstract

BACKGROUND

It has been revealed that mutations can occur spontaneously and naturally in HBV reverse transcriptase (RT) region among untreated patients. These HBV mutants pre-exist as minor viral population in naive patients and can emerge as major viral population, conferring drug resistance and treatment failure.

OBJECTIVES

The aim of this study was to investigate and identify prevalent mutations of RT region of hepatitis B virus genome in patients with chronic hepatitis B (CHB) untreated with antiviral drugs in South-West of Iran.

MATERIALS AND METHODS

A total of 45 cases with CHB who did not receive the treatment of lamivudine and any other antivirus drugs within the last one year were randomly chosen. After sample collection and HBV DNA extraction, RT region was amplified by polymerase chain reaction (PCR). Then PCR products were sequenced and HBV RT region mutations and amino acid changes were analyzed either manually or using web-based programs, on the basis of comparison of the obtained sequences with a set of HBV reference sequences.

RESULTS

A total of 23 (51.1%) mutations and amino acid changes were detected in studied 45 untreated patients. Of these, 3 (6.6%) patients had primary resistance mutation (rtM204I, rtA181T and rtA181S) and 20 (44.4%) patients had secondary resistance mutations.

CONCLUSION

High prevalence of mutations was found in HBV RT region of untreated patients. Most of these mutations were associated with resistance to adefovir and one patient had primary resistance mutation to lamivudine. Awareness of these resistance patterns might help in the antiviral therapy and for predicting clinical outcomes.

摘要

背景

已发现未经治疗的患者中,乙肝病毒逆转录酶(RT)区域可自发自然发生突变。这些乙肝病毒突变体在未感染过乙肝的患者中以少量病毒群体形式预先存在,并可成为主要病毒群体,导致耐药性和治疗失败。

目的

本研究旨在调查和鉴定伊朗西南部未接受抗病毒药物治疗的慢性乙型肝炎(CHB)患者乙肝病毒基因组RT区域的流行突变。

材料与方法

随机选取45例在过去一年未接受拉米夫定及任何其他抗病毒药物治疗的CHB患者。采集样本并提取乙肝病毒DNA后,通过聚合酶链反应(PCR)扩增RT区域。然后对PCR产物进行测序,并根据所得序列与一组乙肝病毒参考序列的比较,手动或使用基于网络的程序分析乙肝病毒RT区域突变和氨基酸变化。

结果

在研究的45例未治疗患者中,共检测到23个(51.1%)突变和氨基酸变化。其中,3例(6.6%)患者有原发性耐药突变(rtM204I、rtA181T和rtA181S),20例(44.4%)患者有继发性耐药突变。

结论

未治疗患者的乙肝病毒RT区域突变发生率较高。这些突变大多与对阿德福韦耐药有关,1例患者对拉米夫定有原发性耐药突变。了解这些耐药模式可能有助于抗病毒治疗和预测临床结果。

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