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慢性乙型肝炎中基础核心启动子和前核心突变的临床意义

Clinical significance of basal core promoter and precore mutations in chronic hepatitis B.

作者信息

Ozgenc O, Ozacar T, Erensoy S, Inan N, Ari A, Kuruuzum Z, Bilgic A

机构信息

Department of Infectious Diseases and Clinical Microbiology, Izmir Teaching and Research Hospital, Izmir, Turkey.

出版信息

Hepatogastroenterology. 2007 Dec;54(80):2319-23.

Abstract

BACKGROUND/AIMS: The mutations in the basal core promoter and precore region of hepatitis B virus genome in hepatitis B e antigen-positive and -negative chronic hepatitis B patients have been described. The reports about their prevalence and clinical significance in the Mediterranean region where D is the predominant genotype, are very limited.

METHODOLOGY

The serum samples were collected from 44 naive chronic hepatitis B patients. For detection of the mutations basal core promoter and precore regions of HBV genome were amplified and sequenced.

RESULTS

All samples were determined as genotype D. Before initiation of treatment basal core promoter mutations were found as 55% (11/20) and 46% (11/24) in HBeAg-positive and -negative patients, respectively (p > 0.5). HBeAg-negative samples were associated with precore mutations (G1896A and G1899A). Three of 20 (15%) patients of HBeAg-positive and seven of 24 (29%) of HBeAg-negative populations showed sustained response to therapy at the 24th month of initiation.

CONCLUSIONS

The presence of precore stop codon mutant in those with sustained response was 89%, overall at the end of therapy. At initiation of therapy basal core promoter mutations were more common in non-responders than responders (65% vs. 20%; p < 0.001). While 23% of cases totally showing sustained response, absence of mutations in the basal core promoter region of hepatitis B virus genotype D may be related to sustained response in patients with chronic hepatitis B.

摘要

背景/目的:已对乙肝e抗原阳性和阴性的慢性乙型肝炎患者乙肝病毒基因组的基础核心启动子和前核心区的突变进行了描述。在以D型为主要基因型的地中海地区,关于这些突变的发生率及其临床意义的报道非常有限。

方法

收集了44例初治慢性乙型肝炎患者的血清样本。通过扩增和测序检测乙肝病毒基因组基础核心启动子和前核心区的突变。

结果

所有样本均确定为D型基因型。在开始治疗前,乙肝e抗原阳性和阴性患者的基础核心启动子突变率分别为55%(11/20)和46%(11/24)(p>0.5)。乙肝e抗原阴性样本与前核心突变(G_{1896}A和G_{1899}A)有关。在开始治疗的第24个月,20例乙肝e抗原阳性患者中有3例(15%)、24例乙肝e抗原阴性患者中有7例(29%)显示出持续应答。

结论

总体而言,在治疗结束时,持续应答患者中前核心终止密码子突变的存在率为89%。在开始治疗时,基础核心启动子突变在无应答者中比应答者更常见(65%对20%;p<0.001)。虽然23%的病例完全显示出持续应答,但D型乙肝病毒基础核心启动子区域无突变可能与慢性乙型肝炎患者的持续应答有关。

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