Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion

Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion
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DOI:
10.1002/hep.510290352
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发表时间:
1999-03-01
期刊:
影响因子:
13.5
通讯作者:
Lok, ASF
Lok, ASF
中科院分区:
医学1区
文献类型:
--
作者:
Chan, HLY;Hussain, M;Lok, ASF

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核心启动子和前C区的突变常见于HBeAg阴性患者,但前C区终止密码子突变仅限于1858位核苷酸为T的B肝炎病毒(HBV)基因型。本研究旨在确定核心启动子和/或前C区突变在HBeAg血清转换中的作用及其对随后肝病病程的影响,并确定在HBV基因型患者中是否更频繁地选择核心启动子突变,从而排除前核心终止密码子突变的发生。对45例慢性HBV感染者的系列血清进行聚合酶链反应(PCR)扩增,并对HBV核心启动子和前C区进行测序。92%的患者在HBeAg血清转换后发生核心启动子或前C区突变:42%仅发生核心启动子变化,38%仅发生前C区终止密码子突变,12%在两个区域都发生变化。73%的患者转氨酶持续正常,只有8%的患者在HBeAg血清转换后转氨酶出现多个突变。核心启动子改变在1858位核苷酸为C的HBV感染患者中明显更常见(91%比27%; P
Mutations in the core promoter and precore regions are frequently found in hepatitis B e antigen (HBeAg)-negative patients, but precore stop codon mutation is restricted to hepatitis B virus (HBV) genotypes that have T at nucleotide 1858, The aims of this study were to determine the role of core promoter and/or precore mutations in HBeAg seroconversion and their impact on the subsequent course of liver disease, and to determine if core promoter mutations are more frequently selected in patients with HBV genotypes that preclude the development of precore stop codon mutation. Serial sera from 45 patients with chronic HBV infection were polymerase chain reaction (PCR)-amplified, and the HBV core promoter and precore regions were sequenced. Ninety-two percent of patients had core promoter or precore mutations after HBeAg seroconversion: 42% had core promoter changes only, 38% had precore stop codon mutations only, and 12% had changes in both regions. Seventy-three percent of the patients had persistently normal aminotransferases, and only 8% had multiple flares in aminotransferases after HBeAg seroconversion, Core promoter changes were significantly more common in patients infected with HBV who have C at nucleotide 1858 (91% vs, 27%; P