乙型肝炎病毒RNA作为HBeAg阴性慢性乙型肝炎对聚乙二醇化干扰

StephenW

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B
Mina S Farag, Margo J H van Campenhout, Maria Pfefferkorn, Janett Fischer, Danilo Deichsel, André Boonstra, Anneke J van Vuuren, Peter Ferenci, Jordan J Feld, Thomas Berg, Bettina E Hansen, Florian van Bömmel, Harry L A Janssen
Author Notes
Clinical Infectious Diseases, Volume 72, Issue 2, 15 January 2021, Pages 202–211, https://doi.org/10.1093/cid/ciaa013
Published:
08 January 2020
Article history

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Abstract
Background

Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.
Methods

HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg.
Results

Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by −1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (−2.0 [1.2] vs −1.5 [1.1] log10 c/mL, P = .04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P = .01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and .80, P < .001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144.
Conclusions

During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up.
Clinical Trials Registration

NCT00114361
Topic:

    biological markers hepatitis b e antigens hepatitis b surface antigens hepatitis b, chronic hepatitis b virus rna peginterferon

StephenW

乙型肝炎病毒RNA作为HBeAg阴性慢性乙型肝炎对聚乙二醇化干扰素α反应的早期预测因子
Mina S Farag，Margo J H van Campenhout，Maria Pfefferkorn，Janett Fischer，Danilo Deichsel，AndréBoonstra，Anneke J van Vuuren，Peter Ferenci，Jordan J Feld，Thomas Berg，Bettina E Hansen，Florian vanBömmel，Harry L A Janssen
作者须知
临床传染病，第21卷，第2期，2021年1月15日，第202-211页，https：//doi.org/10.1093/cid/ciaa013
发布时间：
2020年1月8日
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抽象
背景

乙型肝炎病毒RNA（HBV-RNA）是一种新型的血清生物标志物，与肝内共价闭合环（cccDNA）的转录相关，后者是聚乙二醇化干扰素（PEG-IFN）和功能疗法的新疗法的重要靶标。我们研究了PEG-IFN治疗后的HBV-RNA动力学及其在HBeAg阴性慢性乙型肝炎（CHB）患者中作为应答预测因子的潜在作用。
方法

在一项国际随机对照试验（PARC研究）中，对133名HBeAg阴性CHB患者的HBV-RNA水平进行了测量。患者接受PEG-IFNα-2a治疗48周。从基线到第144周测量HBV-RNA。反应定义为HBV-DNA <2000 IU / mL，第72周时ALT正常化。将HBV-RNA的动力学与HBV-DNA，HBsAg和HBcrAg进行比较。
结果

基线时的平均HBV-RNA为4.4（标准差[SD] 1.2）log10 c / mL。在第12周时，HBV-RNA下降了-1.6（1.1）log10 c / mL。在第12周初，与无反应者相比，HBV-RNA的反应者下降幅度更大（-2.0 [1.2] vs -1.5 [1.1] log10 c / mL，P = 0.04）。高于1700 c / mL（3.2 log10 c / mL）的HBV-RNA水平在第12周的阴性预测值为91％，在第24周的阴性预测值为93％（P = 0.01）。总体而言，HBV-RNA与HBV-DNA和HBcrAg具有更强的相关性（.82和.80，P <.001），与HBsAg的相关性较弱（.25）。第12周时，HBsAg较低（<100 IU / mL）或HBsAg丢失的患者中HBV-RNA显着降低。
结论

在HB-Ag阴性CHB的PEG-IFN治疗期间，HBV-RNA呈快速而显着的下降，这与长期随访时的治疗反应和HBsAg丢失有关。
临床试验注册

NCT00114361
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    生物标志物乙型肝炎e抗原乙型肝炎表面抗原乙型肝炎，慢性乙型肝炎病毒rna聚乙二醇干扰素