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急性乙型肝炎感染与耐药乙型肝炎病毒相关。

Acute hepatitis B infection associated with drug-resistant hepatitis B virus.

机构信息

Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing 302 Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China.

出版信息

J Clin Virol. 2010 Aug;48(4):270-4. doi: 10.1016/j.jcv.2010.05.010. Epub 2010 Jun 26.

Abstract

BACKGROUND

Pre-existing antiviral-resistant hepatitis B virus (HBV) has been associated with primary non-response to lamivudine treatment in patients with chronic hepatitis B, but little is known of the capacity for resistant HBV to cause primary infection.

OBJECTIVE

The study was to investigate if Beijing patients with acute hepatitis B (AHB) are infected with drug-resistant HBV.

STUDY DESIGN

Sera were collected from 201 NA-untreated patients with AHB. Direct polymerase chain reaction (PCR) sequencing was used to screen HBV reverse-transcriptase (RT) domain and clonal sequencing were performed for all resistance-positive samples.

RESULTS

Direct PCR sequencing showed that 14 samples (7.0%) were positive for drug-resistant HBV variants, comprised of 11 with the lamivudine-resistant pattern rtM204I and/or rtM204V in the presence and absence of compensatory mutations rtL80I, rtV173L, and rtL180M; two with the adefovir-resistant pattern rtA181V; and one with the entecavir-resistant pattern rtL180M+rtS202G+rtM204V. Concomitance of resistance variants with wild-type HBV was observed in samples from 13 patients. Clonal sequencing verified direct sequencing results. Furthermore, variants associated with resistance to adefovir or entecavir were found in 3 samples.

CONCLUSIONS

Drug-resistant HBV strains, including those not resistant to lamivudine, are transmissible and can cause acute hepatitis B in China.

摘要

背景

先前存在的抗病毒耐药乙型肝炎病毒(HBV)与慢性乙型肝炎患者拉米夫定治疗的原发性无应答有关,但对于耐药 HBV 引起原发性感染的能力知之甚少。

目的

本研究旨在调查北京地区急性乙型肝炎(AHB)患者是否感染了耐药 HBV。

研究设计

收集了 201 例未经 NA 治疗的 AHB 患者的血清。采用直接聚合酶链反应(PCR)测序法筛选 HBV 逆转录酶(RT)区耐药变异株,并对所有耐药阳性样本进行克隆测序。

结果

直接 PCR 测序显示,14 份(7.0%)样本中存在耐药 HBV 变异株,其中 11 份存在拉米夫定耐药模式 rtM204I 和/或 rtM204V,同时存在或不存在补偿性突变 rtL80I、rtV173L 和 rtL180M;2 份存在阿德福韦耐药模式 rtA181V;1 份存在恩替卡韦耐药模式 rtL180M+rtS202G+rtM204V。在 13 例患者的样本中观察到耐药变异株与野生型 HBV 并存。克隆测序验证了直接测序结果。此外,在 3 份样本中发现了与阿德福韦或恩替卡韦耐药相关的变异株。

结论

包括不耐药拉米夫定的耐药 HBV 株是可传播的,并可在中国引起急性乙型肝炎。

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