聚乙二醇干扰素治疗HBeAg阳性和HBeAg阴性慢性乙型肝炎患者血

StephenW

J Med Virol. 2017 Jan;89(1):130-138. doi: 10.1002/jmv.24601. Epub  2016 Jun 21.
Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.Chuaypen N1, Sriprapun M1, Praianantathavorn K1, Payungporn S1, Wisedopas N2, Poovorawan Y3, Tangkijvanich P4.
Author information

• 1Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand.
• 2Department of Pathology, Chulalongkorn University, Bangkok, Thailand.
• 3Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
• 4Research Unit of Hepatitis and Liver Cancer, Chulalongkorn University, Bangkok, Thailand. [email protected].
  

AbstractThis study was aimed at comparing clinical applicability of serum HBsAg quantification in relation to intrahepatic covalently closed-circular DNA (cccDNA) in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) treated with pegylated interferon (PEG-IFN) monotherapy for 48 weeks. Overall, 32 and 36 patients with HBeAg-positive and HBeAg-negative CHB, respectively were recruited. Paired liver biopsies at baseline and end of therapy were analyzed for cccDNA. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg clearance (for HBeAg-positive CHB) and HBV DNA <2,000 IU/ml (for both groups). The results demonstrated that baseline levels of all viral markers were higher in the HBeAg-positive group than the HBeAg-negative group. Baseline HBsAg correlated with cccDNA in the HBeAg-positive group (r = 0.452, P = 0.009) but not in the HBeAg-negative group (r = 0.018, P = 0.919). However, the magnitude of cccDNA and HBsAg decline at end of treatment was not different between groups. The reduction of HBsAg showed a positive correlation with cccDNA decline in HBeAg-positive and HBeAg-negative CHB (r = 0.544, P = 0.001 and r = 0.364, P = 0.029, respectively). Overall, responders had more decline in cccDNA and HBsAg levels compared with non-responders. Patients with serum HBsAg decline of >1.0 log10  IU/ml during treatment archived VR and HBsAg clearance of 80% and 30%, respectively. In conclusion, serum HBsAg represented a better surrogate marker of intrahepatic cccDNA in patients with HBeAg-positive CHB compared to those with HBeAg-negative CHB. On-treatment, HBsAg reduction of 1.0 log10  IU/mL was associated with a high probability of subsequent VR and HBsAg clearance in patients receiving PEG-IFN therapy. J. Med. Virol. 89:130-138, 2017. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.

KEYWORDS: HBsAg; cccDNA; hepatitis B virus; pegylated-interferon; treatment response

PMID:27307409DOI:10.1002/jmv.24601

StephenW

J Med Virol。 2017 Jan; 89（1）：130-138。 doi：10.1002 / jmv.24601。 2016年6月21日。
聚乙二醇干扰素治疗HBeAg阳性和HBeAg阴性慢性乙型肝炎患者血清HBsAg和肝内cccDNA的动力学
Chuaypen N1，Sriprapun M1，Praianantathavorn K1，Payungporn S1，Wisedopas N2，Poovorawan Y3，Tangkijvanich P4。
作者信息

    1肝炎和肝癌研究单位，朱拉隆功大学，泰国曼谷。
    2病理学，朱拉隆功大学，曼谷，泰国。
    3泰国曼谷朱拉隆功大学医学院临床病毒学卓越中心。
    4肝炎和肝癌研究单位，朱拉隆功大学，泰国曼谷。 [email protected]。

抽象

本研究旨在比较HBeAg阳性和聚乙二醇干扰素（PEG-IFN）单药治疗的HBeAg阴性慢性乙型肝炎（CHB）患者血清HBsAg定量与肝内共价闭环DNA（cccDNA）的临床适用性48周。总体上，招募32和36名HBeAg阳性和HBeAg阴性CHB的患者。在基线和治疗结束时的配对肝活检分析cccDNA。在治疗后48周的病毒学应答（VR）定义为HBeAg清除率（对于HBeAg阳性CHB）和HBV DNA <2,000IU / ml（两组）。结果表明，所有病毒标志物的基线水平在HBeAg阳性组中高于HBeAg阴性组。基线HBsAg与HBeAg阳性组中的cccDNA相关（r = 0.452，P = 0.009），但不在HBeAg阴性组中（r = 0.018，P = 0.919）。然而，治疗结束时cccDNA和HBsAg下降的程度在组间没有差异。 HBsAg的减少与HBeAg阳性和HBeAg阴性CHB中的cccDNA下降呈正相关（r = 0.544，P = 0.001和r = 0.364，P = 0.029）。总体而言，与无应答者相比，应答者的cccDNA和HBsAg水平下降更多。在治疗期间血清HBsAg下降> 1.0 log10 IU / ml的患者归档VR和HBsAg清除率分别为80％和30％。总之，与HBeAg阴性CHB相比，HBeAg阳性CHB患者血清HBsAg代表肝内cccDNA的更好的替代标记。在治疗中，HBsAg降低1.0log 10 IU / mL与接受PEG-IFN治疗的患者中随后的VR和HBsAg清除的高概率相关。 J.Med.Chem。 Virol。 89：130-138,2017。©2016 Wiley Periodicals，Inc.

©2016 Wiley Periodicals，Inc.
关键词：

HBsAg; cccDNA;乙型肝炎病毒;聚乙二醇化干扰素;治疗反应

PMID：
    27307409
DOI：
    10.1002 / jmv.24601