治疗慢性HBV感染对患者报告结局的影响

StephenW

Clin Gastroenterol Hepatol. 2018 Mar 2. pii: S1542-3565(18)30225-8. doi: 10.1016/j.cgh.2018.02.037. [Epub ahead of print]
Effects of Treatment of Chronic HBV Infection on Patient-reported Outcomes.
Younossi ZM1, Stepanova M2, Janssen HLA3, Agarwal K4, Nguyen MH5, Gane E6, Tsai N7, Younossi I2, Racila A2.
Author information

1
    Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA. Electronic address: [email protected].
2
    Center for Outcomes Research in Liver Disease, Washington DC, USA.
3
    Toronto Centre for Liver Disease, University Health Network, Canada.
4
    Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
5
    Stanford University Medical Center, Palo Alto, California, USA.
6
    Auckland Clinical Studies, Auckland, New Zealand.
7
    Queens Medical Center, University of Hawaii, USA.

Abstract
BACKGROUND AND AIM:

Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection.
METHODS:

We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of toll like receptor 7) or placebo. PROs were collected using the Short Form-36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem scoring system before treatment, on treatment weeks 12, 24, and 48.
RESULTS:

We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (level of HBV DNA <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of Chronic Liver Disease Questionnaire and in General Health scores of Short Form-36 (increases of up to 4.9%; P<.05). Patients with a decrease of at least 2.7 log10 IU/mL in level of HBV DNA had substantially larger increases in PRO scores (mean increases of up to 7.2% by week 48; P<.05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (betas values up to 1.6% per log10 IU/mL decrease; P<.05).
CONCLUSIONS:

In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO endpoints in assessments of efficacy and safety in clinical trials of treatments for HBV infection.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:

CLDQ; SF-36; fatigue; health-related quality of life; utility

PMID:
    29505905
DOI:
    10.1016/j.cgh.2018.02.037

StephenW

Clin Gastroenterol Hepatol。 2018年3月2日。pii：S1542-3565（18）30225-8。 doi：10.1016 / j.cgh.2018.02.037。 [电子版提前打印]
治疗慢性HBV感染对患者报告结局的影响。
Younossi ZM1，Stepanova M2，Janssen HLA3，Agarwal K4，Nguyen MH5，Gane E6，Tsai N7，Younossi I2，Racila A2。
作者信息

1
    Inova Fairfax医院医学系肝病中心; Betty和Guy Beatty综合研究中心，Inova健康系统，美国弗吉尼亚州福尔斯彻奇市。电子地址：[email protected]。
2
    美国华盛顿特区肝病研究中心。
3
    加拿大大学健康网络多伦多肝病中心。
4
    英国伦敦国王学院医院肝脏研究所。
五
    斯坦福大学医学中心，美国加利福尼亚州帕洛阿尔托。
6
    奥克兰临床研究，新西兰奥克兰。
7
    皇后医学中心，美国夏威夷大学。

抽象
背景和目的：

慢性乙型肝炎病毒（HBV）感染会导致肝脏疾病和肝硬化。尚不清楚慢性HBV感染的治疗如何影响患者报告的结局（PRO）。我们旨在评估治疗慢性HBV感染的患者中PROs的变化。
方法：

我们收集并分析了2015年至2017年期间入选了2项国际2期盲法对照临床试验的242例慢性HBV感染（无进展性纤维化或肝硬化）患者的PRO数据。在这些试验中，患者接受了批准的口服抗病毒治疗方案（替诺福韦，恩替卡韦，阿德福韦酯，拉米夫定或替比夫定），然后随机分配给予vesatolimod组（口服受体激动剂受体7）或安慰剂。在治疗前12周，24周和48周，使用简表-36，慢性肝病问卷，工作生产力和活动障碍：特定健康问题评分系统收集PRO。
结果：

我们没有观察到接受vesatolimod与安慰剂的患者之间PRO的显着差异。在基线时，病毒抑制的患者（HBV DNA水平<20 IU / mL）具有更高的PRO评分（高达PRO范围大小的+ 10.6％）。在治疗期间，慢性肝病调查问卷的一些领域和Short Form-36的一般健康评分（增加至4.9％; P <0.05）的评分显着增加。 HBV DNA水平下降至少2.7 log10 IU / mL的患者PRO评分有显着增加（第48周平均增加至7.2％; 22位研究PRO中10位P <0.05）。在多变量分析中，病毒载量的减少与PROs增加独立相关（每log10 IU / mL下降，β值高达1.6％; P <0.05）。
结论：

在对2期试验数据的分析中，我们将慢性HBV感染的积极治疗与PRO评分增加联系起来。这些发现支持将PRO终点纳入HBV感染治疗临床试验疗效和安全性评估。

版权所有©2018 AGA研究所。由Elsevier Inc.出版。保留所有权利。
关键词：

CLDQ; SF-36;疲劳;健康相关的生活质量;效用

结论：
    29505905
DOI：
    10.1016 / j.cgh.2018.02.037