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东亚乙型肝炎病毒携带者中与病毒复制和肝损伤相关的核心启动子突变及基因型

Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers.

作者信息

Lindh M, Hannoun C, Dhillon A P, Norkrans G, Horal P

机构信息

Department of Clinical Virology, Göteborg University, S-413 46 Göteborg, Sweden.

出版信息

J Infect Dis. 1999 Apr;179(4):775-82. doi: 10.1086/314688.

Abstract

Virus load and liver damage, as measured by quantitative polymerase chain reaction and histology activity index, were related to genotype and core promoter mutations in 43 chronic hepatitis B virus (HBV) carriers of East Asian origin. T-1762 mutants were more frequent in genotype C strains and were associated with more inflammation (P=.0036) and fibrosis (P=.0088) of the liver but not with hepatitis B e antigen (HBeAg) status or virus load. Conversely, precore mutations were associated with less liver inflammation (P=. 08), which was linked to HBeAg negativity and lower viral replication. Carriers with genotype C were more often HBeAg positive (P=.03) with precore wild type strains and more-severe liver inflammation (P=.009) than were those with genotype B. These findings suggest that pathogenic differences between genotypes may exist and that the T-1762 mutation may be useful as a marker for progressive liver damage but seem to contradict that down-regulation of HBeAg production is the major effect of this mutation.

摘要

通过定量聚合酶链反应和组织学活性指数测定,东亚裔43例慢性乙型肝炎病毒(HBV)携带者的病毒载量和肝损伤与基因型及核心启动子突变有关。T-1762突变体在C基因型毒株中更常见,并且与肝脏更多炎症(P = 0.0036)和纤维化(P = 0.0088)相关,但与乙肝e抗原(HBeAg)状态或病毒载量无关。相反,前核心突变与肝脏炎症较少(P = 0.08)相关,这与HBeAg阴性和较低的病毒复制有关。与B基因型携带者相比,C基因型携带者在前核心野生型毒株中更常出现HBeAg阳性(P = 0.03),且肝脏炎症更严重(P = 0.009)。这些发现表明不同基因型之间可能存在致病差异,并且T-1762突变可能作为进行性肝损伤的一个标志物,但这似乎与该突变的主要作用是下调HBeAg产生相矛盾。

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