血清学转换前存在乙肝病毒核心启动子突变可预测HBeAg消失后病毒持续复制。

Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBeAg loss.

作者信息

Ferns R Bridget, Naoumov Nikolai V, Gilson Richard J, Tedder Richard S

机构信息

Centre for Virology, Department of Infection, University College, Windeyer Building, 46 Cleveland Street, London W1T 4JF, United Kingdom.

出版信息

J Clin Virol. 2007 Jul;39(3):199-204. doi: 10.1016/j.jcv.2007.04.008. Epub 2007 May 29.

Abstract

BACKGROUND

In patients with chronic hepatitis B virus (HBV) infection DNA levels do not always fall after anti-hepatitis B e (anti-HBe) seroconversion.

OBJECTIVES

To follow longitudinally through HB e antigen (HBeAg) loss HBV DNA levels and core promoter/precore sequences in a cohort of 21 chronic HBV carriers.

STUDY DESIGN

Treatment-naïve HBeAg seropositive HBV carriers were monitored through HBeAg loss for between 2 and 22 years (mean 9.3). Core promoter/precore sequences, genotypes, HBV DNA levels and HBe status were determined.

RESULTS

Patients were grouped into those in whom serum/plasma HBV DNA remained high after HBeAg loss (group 1, n=11; HBV DNA>5log(10)IU/ml) and those in whom HBV DNA declined (group 2, n=10). Re-appearance of HBeAg was seen in seven group 1 patients. Pre-seroconversion mutations in the core promoter region including A1762T and/or G1764A were detected more frequently in group 1 (P=0.031). Overall sequence changes at sites other than 1762/1764 were more common post-seroconversion in group 1 than group 2 patients (P=0.037).

CONCLUSIONS

The presence of core promoter mutations prior to HBeAg loss identified those patients in whom HBV DNA persisted at high levels and was associated with temporary re-emergence of serum HBeAg. These patients may benefit from early anti-viral treatment.

摘要

背景

在慢性乙型肝炎病毒(HBV)感染患者中,抗乙型肝炎e抗原(抗-HBe)血清学转换后,DNA水平并非总是下降。

目的

在一组21例慢性HBV携带者中,纵向追踪HBe抗原(HBeAg)消失后的HBV DNA水平及核心启动子/前核心序列。

研究设计

对未经治疗的HBeAg血清学阳性HBV携带者进行HBeAg消失的监测,时间为2至22年(平均9.3年)。测定核心启动子/前核心序列、基因型、HBV DNA水平及HBe状态。

结果

患者被分为HBeAg消失后血清/血浆HBV DNA仍高的患者(第1组,n = 11;HBV DNA>5log(10)IU/ml)和HBV DNA下降的患者(第2组,n = 10)。在第1组的7例患者中观察到HBeAg再次出现。第1组中核心启动子区域包括A1762T和/或G1764A的血清学转换前突变检出频率更高(P = 0.031)。第1组患者血清学转换后1762/1764以外位点的总体序列变化比第2组更常见(P = 0.037)。

结论

HBeAg消失前核心启动子突变的存在可识别出那些HBV DNA持续高水平的患者,并与血清HBeAg的暂时再现相关。这些患者可能从早期抗病毒治疗中获益。

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