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B型乙肝病毒比C型乙肝病毒更早出现拉米夫定耐药性。

Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C.

作者信息

Hsieh Ting-Hui, Tseng Tai-Chung, Liu Chun-Jen, Lai Ming-Yang, Chen Pei-Jer, Hsieh Hsin-Ling, Chen Ding-Shinn, Kao Jia-Horng

机构信息

Division of Hepatology, Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.

出版信息

Antivir Ther. 2009;14(8):1157-63. doi: 10.3851/IMP1454.

DOI:10.3851/IMP1454
PMID:20032545
Abstract

BACKGROUND

Hepatitis B virus (HBV) genotype B and C seem not to affect the therapeutic response to lamivudine (3TC). Whether a given genotype has an earlier emergence of 3TC resistance remains unclear. We thus conducted this study to elucidate the association of HBV genotype with the emergence of 3TC-resistant strains in Taiwanese patients.

METHODS

Forty chronic hepatitis B patients who developed resistance after 3TC therapy were retrospectively enrolled. HBV genotype, serum alanine aminotransferase (ALT) and HBV DNA levels were determined at baseline. The presence of 3TC-resistant mutations was confirmed by direct sequencing whenever biochemical breakthrough developed.

RESULTS

The distribution of HBV genotype B and C in 40 patients receiving 3TC therapy were 60% and 40%, respectively. The mean interval to detect 3TC-resistant strain was 19.6 +/-1.7 months. By using multivariate analysis, HBV genotype B and higher pre-treatment HBV DNA level were independently associated with earlier detection of 3TC-resistant strains. In addition, genotype B was significantly associated with development of 3TC resistance within the first 12 months of 3TC therapy compared with genotype C (odds ratio 8.27; P=0.004).

CONCLUSIONS

Compared with HBV genotype C, genotype B appears to have an earlier biochemical resistance to 3TC than genotype C. Therefore, more frequent monitoring of viral load or genotypical resistance might be needed for patients with HBV genotype B infection receiving 3TC therapy, especially during the first year.

摘要

背景

乙肝病毒(HBV)B型和C型似乎不影响对拉米夫定(3TC)的治疗反应。某一特定基因型是否会更早出现3TC耐药尚不清楚。因此,我们开展了本研究以阐明HBV基因型与台湾患者中3TC耐药株出现之间的关联。

方法

回顾性纳入40例接受3TC治疗后出现耐药的慢性乙肝患者。在基线时测定HBV基因型、血清丙氨酸转氨酶(ALT)和HBV DNA水平。每当出现生化突破时,通过直接测序确认3TC耐药突变的存在。

结果

40例接受3TC治疗的患者中,HBV B型和C型的分布分别为60%和40%。检测到3TC耐药株的平均间隔时间为19.6±1.7个月。通过多因素分析,HBV B型和治疗前较高的HBV DNA水平与更早检测到3TC耐药株独立相关。此外,与C型相比,B型在3TC治疗的前12个月内出现3TC耐药的情况显著更多(优势比8.27;P = 0.004)。

结论

与HBV C型相比,B型似乎比C型对3TC出现生化耐药更早。因此,接受3TC治疗的HBV B型感染患者可能需要更频繁地监测病毒载量或基因型耐药情况,尤其是在第一年。

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