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来自伊朗未经治疗的慢性乙肝患者的乙肝病毒(HBV)逆转录酶蛋白中与药物相关的突变模式。

Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-naïve chronic HBV patients.

作者信息

Mahabadi Mostafa, Norouzi Mehdi, Alavian Seyed Moayyed, Samimirad Katayoon, Azad Talat Mokhtari, Saberfar Esmaeil, Mahmoodi Mahmood, Ramezani Fatemeh, Karimzadeh Hadi, Malekzadeh Reza, Montazeri Ghodrat, Nejatizadeh Azim, Ziaee Masood, Abedi Farshid, Ataei Behrooz, Yaran Majid, Sayad Babak, Hossein Somi Mohammad, Sarizadeh Gholamreza, Sanei-Moghaddam Ismaeil, Mansour-Ghanaei Fariborz, Rafatpanah Houshang, Pourhosseingholi Mohammad Amin, Keyvani Hossain, Kalantari Ebrahim, Saberifiroozi Mehdi, Ali Judaki Mohammad, Ghamari Shiva, Daram Maryam, Fazeli Zeinab, Goodarzi Zahra, Khedive Abolfazl, Moradi Abdolvahab, Jazayeri Seyed Mohamad

机构信息

Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran.

出版信息

Hepat Mon. 2013 Jan 20;13(1):e6712. doi: 10.5812/hepatmon.6712. Print 2013 Jan.

Abstract

BACKGROUND

Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness.

OBJECTIVES

The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments.

MATERIALS AND METHODS

Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database.

RESULTS

All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively.

CONCLUSIONS

RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

摘要

背景

免疫调节剂和核苷酸类似物已在全球范围内用于治疗慢性乙型肝炎病毒(HBV)感染。然而,耐药性的产生是其长期疗效的主要限制因素。

目的

本研究旨在对未接受任何抗病毒治疗的伊朗慢性HBV携带者中乙型肝炎病毒逆转录酶(RT)蛋白变异进行特征分析。

材料与方法

对325例慢性非活动性携带者患者的乙型肝炎病毒部分RT基因进行扩增并直接测序。与数据库中获得的序列相比,鉴定核苷酸/氨基酸替换。

结果

所有菌株均属于D基因型。共发现365个氨基酸替换。与拉米夫定、阿德福韦、替比夫定和恩替卡韦相关的突变分别出现在4%(n = 13)、17.23%(n = 56)、2.45%(n = 8)和2.76%(n = 9)的患者中。

结论

RT突变体确实自然发生,并且可以在从未接受过抗病毒治疗的HBV携带者中发现。然而,在未经治疗的伊朗慢性HBV患者中,与耐药相关的突变高于以前发表的其他研究。在开始治疗前,应对慢性HBV患者进行密切监测,以选择最佳治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cc3/3626233/0ebc43311aad/hepatmon-13-01-6712-i001.jpg

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