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加大丙型肝炎防治力度以实现消除目标:全球数学模型。

Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model.

机构信息

MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.

Division of Infectious Diseases, St Mary's Hospital, Imperial College London, London, UK.

出版信息

Lancet. 2019 Mar 30;393(10178):1319-1329. doi: 10.1016/S0140-6736(18)32277-3. Epub 2019 Jan 29.

Abstract

BACKGROUND

The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.

METHODS

We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions.

FINDINGS

By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan.

INTERPRETATION

Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic.

FUNDING

Wellcome Trust.

摘要

背景

丙型肝炎病毒 (HCV) 治疗的革命性进展——直接作用抗病毒药物 (DAA) 的出现——引发了国际社会消除这一公共卫生威胁的兴趣。2017 年,世界卫生组织为此制定了 2030 年消除目标。我们评估了公共卫生干预措施对全球 HCV 流行的影响,并研究了世界卫生组织的消除目标是否能够实现。

方法

我们开发了一个全球 HCV 流行的动态传播模型,该模型经过校准,可适用于 190 个国家,其中纳入了人口统计学、静脉注射吸毒者 (PWID)、治疗和预防规划的当前覆盖范围、疾病自然史、HCV 流行率和 HCV 相关死亡率的数据。我们通过考虑以下六种情景来估计扩大降低传播风险、增加治疗机会和增加 HCV 感染筛查的干预措施的全球影响:不改变现有诊断或治疗水平;依次增加以下干预措施:血液安全和感染控制、PWID 减少伤害、在诊断时提供 DAA 以及扩大筛查以增加诊断人数;以及不引入 DAA 的情景(即仅使用聚乙二醇干扰素和口服利巴韦林进行治疗),以研究 DAA 使用的效果。我们在敏感性分析中研究了改变这些干预措施的覆盖范围或影响的效果,还评估了从一揽子干预措施中去除某些关键国家对全球流行情况的影响。

发现

到 2030 年,降低非 PWID 人群传播风险 80%和增加 40%PWID 获得减少伤害服务的覆盖面,可避免 1410 万例(95%可信区间 13.0-15.2)新感染。在所有国家对诊断时提供 DAA,可预防 64 万例(62 万-67 万)肝硬化和肝癌死亡。全面的预防、筛查和治疗干预一揽子计划可避免 1510 万例(13.8-16.1)新感染和 150 万例(1.4-1.6)肝硬化和肝癌死亡,与 2015 年基线相比,发病率降低 81%(78-82%),死亡率降低 61%(60-62%)。这达到了世界卫生组织 80%的发病率降低目标,但距离 65%的死亡率降低目标还差一点,这一目标可以在 2032 年达到。全球负担的减轻取决于预防干预措施的成功、扩大筛查和在包括中国、印度和巴基斯坦在内的关键高负担国家取得进展。

解释

进一步改善血液安全和感染控制、扩大或建立 PWID 减少伤害服务以及广泛筛查 HCV 并同时进行治疗,这是减少 HCV 负担的必要条件。这些发现应能为正在进行的消除 HCV 流行的全球行动提供信息。

资金

惠康信托基金会。

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