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507 例中国急、慢性乙型肝炎患者乙型肝炎病毒基因型和基本核心启动子/前 C 区突变的特征及其临床意义。

Features and clinical implications of hepatitis B virus genotypes and mutations in basal core promoter/precore region in 507 Chinese patients with acute and chronic hepatitis B.

机构信息

Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China.

出版信息

J Clin Virol. 2010 Mar;47(3):243-7. doi: 10.1016/j.jcv.2009.12.013. Epub 2010 Jan 15.

Abstract

BACKGROUND

The association of hepatitis B virus (HBV) genotypes and basal core promoter (BCP) and precore (PC) mutations with the clinical characteristics is increasingly recognized.

OBJECTIVE

To investigate virologic features and clinical implications of HBV genotypes, BCP and PC mutations between large-size patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB).

STUDY DESIGN

One hundred and eighty-two AHB patients and 325 CHB patients were investigated. HBV genotypes and BCP/PC mutations were determined by direct sequencing. Mutations at 10 interested sites of the BCP/PC region were compared between the two groups of patients.

RESULTS

AHB patients had a significantly higher ratio of genotype B to C than CHB patients (37.4-62.6% vs. 16.6-83.4%, P<0.001). The prevalence of BCP/PC wild-type virus was 60.4% in AHB patients in contrast to 28.9% in CHB patients. Significantly lower prevalence of A1762T, G1764A, G1896A, and G1899A but higher prevalence of T1758C was found in AHB patients. Interestingly, T1758C and A1762T/G1764A appeared mutual restraint. Genotype B virus had lower BCP mutation frequency and similar PC mutation frequency compared to genotype C virus. AHB patients with BCP/PC mutant virus had higher viral load, whereas CHB patients with BCP/PC mutant virus had lower viral load and elevated alanine aminotransferase, in comparison with those with the wild-type virus.

CONCLUSION

Patients with genotype B virus, BCP/PC wild-type virus or T1758C mutant virus were more susceptible to develop AHB, whereas high prevalence of the BCP/PC mutations was associated with CHB development.

摘要

背景

乙型肝炎病毒(HBV)基因型、基本核心启动子(BCP)和前核心(PC)突变与临床特征的关联正日益得到认识。

目的

研究大体积急性乙型肝炎(AHB)和慢性乙型肝炎(CHB)患者中 HBV 基因型、BCP 和 PC 突变的病毒学特征及其临床意义。

研究设计

共调查了 182 例 AHB 患者和 325 例 CHB 患者。通过直接测序确定 HBV 基因型和 BCP/PC 突变。比较两组患者 BCP/PC 区域 10 个感兴趣位点的突变情况。

结果

AHB 患者乙型肝炎病毒基因型 B 的比例明显高于 CHB 患者(37.4%-62.6%比 16.6%-83.4%,P<0.001)。与 CHB 患者相比,AHB 患者 BCP/PC 野生型病毒的患病率为 60.4%,而 CHB 患者为 28.9%。在 AHB 患者中,A1762T、G1764A、G1896A 和 G1899A 的发生率明显较低,而 T1758C 的发生率较高。有趣的是,T1758C 和 A1762T/G1764A 似乎相互抑制。与基因型 C 病毒相比,基因型 B 病毒的 BCP 突变频率较低,PC 突变频率相似。与野生型病毒相比,BCP/PC 突变病毒的 AHB 患者病毒载量更高,而 CHB 患者的病毒载量较低,丙氨酸氨基转移酶升高。

结论

基因型 B 病毒、BCP/PC 野生型病毒或 T1758C 突变病毒的患者更容易发生 AHB,而 BCP/PC 突变的高发生率与 CHB 的发生有关。

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