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青少年和成人丙型肝炎病毒感染筛查:美国预防服务工作组的最新证据报告和系统评价

Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

作者信息

Chou Roger, Dana Tracy, Fu Rongwei, Zakher Bernadette, Wagner Jesse, Ramirez Shaun, Grusing Sara, Jou Janice H

机构信息

Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland.

Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland.

出版信息

JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.20788.

DOI:10.1001/jama.2019.20788
PMID:32119034
Abstract

IMPORTANCE

A 2013 review for the US Preventive Services Task Force (USPSTF) of hepatitis C virus (HCV) screening found interferon-based antiviral therapy associated with increased likelihood of sustained virologic response (SVR) and an association between achieving an SVR and improved clinical outcomes. New direct-acting antiviral (DAA) regimens are available.

OBJECTIVE

To update the 2013 review on HCV screening to inform the USPSTF.

DATA SOURCES

Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through February 2019, with surveillance through September 2019.

STUDY SELECTION

Randomized clinical trials (RCTs) and nonrandomized treatment studies of HCV screening and DAA therapy; cohort studies on screening, antiviral therapy, and the association between an SVR after antiviral therapy and clinical outcomes.

DATA EXTRACTION AND SYNTHESIS

One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.

MAIN OUTCOMES AND MEASURES

Mortality, morbidity, quality of life, screening and treatment harms, and screening diagnostic yield.

RESULTS

Eight RCTs of DAA therapy vs placebo or an outdated antiviral regimen, 48 other treatment studies, and 33 cohort studies, with a total of 179 230 participants, were included. No study evaluated effects of HCV screening vs no screening. One new study since the 2013 review (n = 5917) found similar diagnostic yield of risk-based screening (sensitivity, 82%; number needed to screen to identify 1 HCV case, 15) and birth cohort screening (sensitivity, 76%; number needed to screen, 29), assuming perfect implementation. Ten open-label studies (n = 3292) reported small improvements in some quality-of-life and functional outcomes (eg, less than 3 points on the 0 to 100 36-Item Short Form Health Survey physical and mental component summary scales) after DAA treatment compared with before treatment. Two cohort studies (n = 24 686) found inconsistent associations of antiviral therapy vs no therapy with risk of hepatocellular carcinoma. Forty-nine treatment studies (n = 10 181) found DAA regimens associated with pooled SVR rates greater than 95% across genotypes, and low short-term rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%). An SVR after antiviral therapy was associated with decreased adjusted risk of all-cause mortality (13 studies, n = 36 986; pooled hazard ratio [HR], 0.40 [95% CI, 0.28-0.56) and hepatocellular carcinoma (20 studies, n = 84 491; pooled HR, 0.29 [95% CI, 0.23 to 0.38]) vs no SVR.

CONCLUSIONS AND RELEVANCE

Direct evidence on the effects of HCV screening on clinical outcomes remains unavailable, but DAA regimens were associated with SVR rates greater than 5% and few short-term harms relative to older antiviral therapies. An SVR after antiviral therapy was associated with improved clinical outcomes compared with no SVR.

摘要

重要性

2013年美国预防服务工作组(USPSTF)对丙型肝炎病毒(HCV)筛查的一项综述发现,基于干扰素的抗病毒治疗与持续病毒学应答(SVR)可能性增加相关,且实现SVR与改善临床结局之间存在关联。新的直接抗病毒药物(DAA)方案已可供使用。

目的

更新2013年关于HCV筛查的综述,为USPSTF提供信息。

数据来源

截至2019年2月的Ovid MEDLINE、Cochrane对照试验中央注册库和Cochrane系统评价数据库,并持续监测至2019年9月。

研究选择

HCV筛查和DAA治疗的随机临床试验(RCT)及非随机治疗研究;关于筛查、抗病毒治疗以及抗病毒治疗后SVR与临床结局之间关联的队列研究。

数据提取与合成

一名研究人员提取数据;另一名检查准确性。两名研究人员独立评估研究质量。

主要结局和指标

死亡率、发病率、生活质量、筛查和治疗的危害以及筛查诊断率。

结果

纳入了8项DAA治疗与安慰剂或过时抗病毒方案对比的RCT、48项其他治疗研究以及33项队列研究,共计179230名参与者。没有研究评估HCV筛查与不筛查的效果。自2013年综述以来的一项新研究(n = 5917)发现,假设完美实施,基于风险的筛查(敏感性82%;识别1例HCV病例所需筛查人数为15)和出生队列筛查(敏感性76%;所需筛查人数为29)的诊断率相似。10项开放标签研究(n = 3292)报告称,与治疗前相比,DAA治疗后一些生活质量和功能结局有小幅改善(例如,在0至100的36项简短健康调查身体和精神成分汇总量表上改善不到3分)。两项队列研究(n = 24686)发现抗病毒治疗与未治疗相比,肝细胞癌风险的关联不一致。49项治疗研究(n = 10181)发现,DAA方案在各基因型中的汇总SVR率大于95%,严重不良事件短期发生率低(1.9%),因不良事件停药率低(0.4%)与未实现SVR相比,抗病毒治疗后实现SVR与全因死亡率调整风险降低相关(13项研究,n = 36986;汇总风险比[HR],0.40[95%CI,0.28 - 0.56])和肝细胞癌风险降低相关(20项研究,n = 84491;汇总HR,0.29[95%CI,0.23至0.38])。

结论与关联

关于HCV筛查对临床结局影响的直接证据仍然缺乏,但与较旧的抗病毒疗法相比,DAA方案的SVR率大于95%且短期危害较少。与未实现SVR相比,抗病毒治疗后实现SVR与改善临床结局相关。

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