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定量乙肝表面抗原联合乙肝e抗原作为聚乙二醇干扰素α-2a延长治疗期间乙肝e抗原阳性慢性乙型肝炎病毒学持续应答预测指标的研究

Quantitative hepatitis B surface antigen combined with hepatitis B e antigen as sustained virological response predictors during extended therapy with Peginterferon alfa-2a for hepatitis B e antigen-positive chronic hepatitis B.

作者信息

Chen Jie, Zhang Dong-Hua, Xu Cheng-Run, Zhu Ming-Yu, Yang Zhi-Tao, Gong Qi-Ming, Yu De-Min, Zhang Xin-Xin

机构信息

Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.

Department of Infection Diseases, Southeast Hospital, Xiamen University, Zhangzhou 363000, People's Republic of China.

出版信息

J Clin Virol. 2015 Nov;72:88-94. doi: 10.1016/j.jcv.2015.09.012. Epub 2015 Oct 9.

Abstract

BACKGROUND

The best strategy for chronic hepatitis B patients with poor response to 48 weeks of Peginterferon-based therapy has been controversial and the predictive value of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels for determining the sustained virological response (SVR) of these patients is uncertain.

OBJECTIVES

To optimize management of these patients and evaluate the use of these serobiomarkers to predict SVR.

STUDY DESIGN

Eighty-one patients with an unsatisfactory response after 48 weeks of Peginterferon-based therapy were treated with extended Peginterferon therapy with or without nucleo(s) tide analogues (NAs), for a total of 96 weeks of Peginterferon treatment. HBsAg, HBeAg and HBV DNA levels were measured serially during the treatment and follow-up.

RESULTS AND CONCLUSIONS

Twenty-six of 81 patients (32.1%) attained SVR during the 72-week follow-up. The SVR rate was not statistically different between groups receiving 1-year prolongation of Peginterferon with or without NAs. The serum HBsAg cut-off of 1800IU/mL at week 48 had area under curve (AUC) of 0.727, and the serum HBsAg cut-off of 1500IU/mL, combined with HBeAg loss at week 72, had AUC of 0.753 to predict SVR during the follow-up. In conclusion, extended treatment with Peginterferon with or without NAs for patients with unsatisfactory response after 48 weeks of Peginterferon-based therapy is a promising strategy to achieve SVR, and quantitative serum HBsAg at week 48 and HBsAg level combined with HBeAg loss at week 72 of therapy can predict SVR to prolongation therapy with Peginterferon.

摘要

背景

对于聚乙二醇干扰素治疗48周疗效不佳的慢性乙型肝炎患者,最佳治疗策略一直存在争议,乙肝表面抗原(HBsAg)、乙肝e抗原(HBeAg)和乙肝病毒(HBV)DNA水平对确定这些患者持续病毒学应答(SVR)的预测价值尚不确定。

目的

优化这些患者的管理,并评估这些血清生物标志物预测SVR的应用价值。

研究设计

81例接受聚乙二醇干扰素治疗48周疗效不佳的患者接受了延长聚乙二醇干扰素治疗,联合或不联合核苷(酸)类似物(NA),聚乙二醇干扰素治疗总疗程达96周。在治疗及随访期间连续检测HBsAg、HBeAg和HBV DNA水平。

结果与结论

81例患者中有26例(32.1%)在72周随访期间达到SVR。接受聚乙二醇干扰素延长治疗1年联合或不联合NA的组间SVR率无统计学差异。第48周时血清HBsAg临界值为1800IU/mL,曲线下面积(AUC)为0.727;第48周时血清HBsAg临界值为1500IU/mL,联合第72周时HBeAg消失,预测随访期间SVR的AUC为0.753。结论:对于聚乙二醇干扰素治疗48周疗效不佳的患者,联合或不联合NA延长聚乙二醇干扰素治疗是实现SVR的一种有前景的策略,治疗第48周时的血清HBsAg定量以及治疗第72周时的HBsAg水平联合HBeAg消失情况可预测聚乙二醇干扰素延长治疗的SVR。

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