聚乙二醇干扰素联合替诺福韦联合治疗对初治乙型肝炎患者e

StephenW

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients with Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience
Chengguang Hu  1 , Yangda Song  1 , Cuirong Tang  1 , Meng Li  1 , Junwei Liu  2 , Jia Liu  3 , Minjun Liao  1 , Fuyuan Zhou  2 , Yong-Yuan Zhang  4 , Yuanping Zhou  5
Affiliations
Affiliations

    1
    Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    2
    Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    3
    Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    4
    HBVtech, Germantown, MD, USA. Electronic address: [email protected].
    5
    Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].

    PMID: 33516527 DOI: 10.1016/j.clinthera.2020.12.022

Abstract

Purpose: The loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.

Methods: A total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ2 test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan-Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.

Findings: At week 72, the Kaplan-Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log10 IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.

Implications: A 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log10 IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.

Keywords: combination therapy; hepatitis B surface antigen clearance; pegylated interferon; tenofovir disoproxil fumarate.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

StephenW

聚乙二醇干扰素联合替诺福韦联合治疗对初治乙型肝炎患者e抗原阳性的慢性乙型肝炎患者乙型肝炎高级乙肝表面抗原损失的影响：真实经验
胡成光1，杨大松1，唐翠荣1，李萌1，刘俊伟2，刘佳3，廖敏俊1，周福源2，张永元4，周原平5
隶属关系
隶属关系

    1个
    南方医科大学南方医院消化内科，广州；南方医科大学南方医院传染病与肝病科，广东广州
    2
    南方医科大学南方医院传染病与肝病科，广东广州
    3
    南方医科大学附属南方医院药剂科，广州
    4
    HBVtech，美国马里兰州日耳曼敦。电子地址：[email protected]。
    5
    南方医科大学南方医院消化内科，广州电子地址：[email protected]。

    PMID：33516527 DOI：10.1016 / j.clinthera.2020.12.022

抽象

目的：慢性乙型肝炎（CHB）患者的血清乙型肝炎表面抗原（HBsAg）的丢失被认为是理想的临床结果，但目前的治疗标准很少能达到。我们评估了在现实世界中接受聚乙二醇干扰素（Peg-IFN）联合替诺福韦富马酸替诺福韦酯（TDF）或每种药物单药治疗的CHB患者的临床队列中诱导HBsAg血清清除的有效性。

方法：总共330名CHB患者被分配接受Peg-IFN加TDF治疗48周（Peg-IFN加TDF治疗组），单独接受Peg-IFN治疗48周（Peg-IFN治疗组），或单独接受TDF 144周治疗（TDF组）。主要终点是在第72周时达到HBsAg血清清除的患者百分比。使用χ2检验分类变量或使用1向ANOVA进行连续变量比较与基线特征和治疗数据的差异。进行Kaplan-Meier测试以比较3组之间的HBsAg损失。使用AUC曲线定量区分反应者和非反应者。根据定义为J =敏感性+特异性-1的Youden J统计量选择最佳临界值。

结果：在第72周时，Peg-IFN加TDF组的Kaplan-Meier累积HBsAg损失为11.5％，Peg-IFN组为5.7％，TDF组为0％。在Peg-IFN加TDF和Peg-IFN组中，HBsAg丢失的患者比例相当（P = 0.143），但两者均显着高于TDF组（P = 0.000和P = 0.010）。此外，与TDF组相比，联合组和Peg-IFN组的患者血清HBsAg <100 IU / mL显着更高（32.7％vs 23.6％vs 9.2％； P <0.001），但无显着差异在HBsAg <1000 IU / mL的患者中，血清HBV DNA和乙型肝炎e抗原血清转化率检测不到。如果在治疗第24周将HBsAg水平从基线降低> 1.5 log10 IU / mL，我们的模型将预测在第72周的血清HBsAg丧失（AUC = 0.846），这是预测该人群中HBsAg丧失的最佳时间点。

潜在影响：与TDF单一疗法相比，Peg-IFN和TDF联合疗法的48周疗程可导致血清HBsAg水平大大降低，从而导致HBsAg丢失率显着提高。在第24周时HBsAg急剧下降> 1.5 log10 IU / mL的患者预示在第72周出现HBsAg丧失的可能性更高。

关键词：联合治疗；乙肝表面抗原清除；聚乙二醇干扰素替诺福韦酯富马酸酯。

版权所有©2021作者。由Elsevier Inc.出版。保留所有权利。

StephenW

https://www.clinicaltherapeutics ... 2918(21)00006-0/pdf