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瑞士阿片类激动剂治疗方案中丙型肝炎病毒的消除 - SAMMSU 队列。

Hepatitis C virus elimination in Swiss opioid agonist therapy programmes - the SAMMSU cohort.

机构信息

Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital Aarau, Switzerland.

Arud Centre for Addiction Medicine, Zurich, Switzerland.

出版信息

Swiss Med Wkly. 2021 Mar 4;151:w20460. doi: 10.4414/smw.2021.20460. eCollection 2021 Mar 1.

DOI:10.4414/smw.2021.20460
PMID:33705563
Abstract

BACKGROUND

Hepatitis C virus (HCV) infections in Switzerland are mainly related to intravenous drug use. Since 2017, all patients with chronic hepatitis C can be treated with direct-acting antivirals (DAAs) irrespective of fibrosis stage. In March 2019, the Federal Office of Public Health (FOPH) published guidelines for HCV management in people who use drugs. To achieve HCV elimination by 2030, 80% treatment uptake is necessary.

AIM

To evaluate the benefit of interferon-based and interferon-free HCV treatment in patients on opioid agonist therapy (OAT) and monitor HCV elimination, a 2-year study commissioned by the FOPH and conducted within the Swiss Association for the Medical Management in Substance Users (SAMMSU) cohort was performed.

METHODS

Since 2014, the SAMMSU cohort has recruited OAT patients from eight different centres throughout Switzerland. In addition to yearly follow up, cross-sectional data were collected at the time-points 1 May 2017, 1 May 2018 and 1 May 2019. HCV treatment uptake, adherence and success, as well as reinfection rates, the effect of early versus late treatment and the efficacy of the “treatment-as-prevention” approach were analysed.

RESULTS

Between 1 May 2017 and 1 May 2019, the number of patients enrolled into the SAMMSU cohort increased from 623 to 900: 78% were male, the median age was 45 years, 81% had ever used intravenous drugs, 13% were human immunodeficiency virus (HIV) positive and 66% were HCV antibody positive. HCV treatment up to 2012 was exclusively interferon based (maximum 21 patients/year) and since 2016 exclusively interferon free (102 patients in 2017). Treatment success increased from 57% (112/198; interferon based) to 97% (261/268; interferon free) irrespective of cirrhosis or prior non-response to interferon. Simultaneously, treatments became shorter and better tolerated in the interferon-free era, resulting in fewer preterm stops (17% vs 1%) and adherence problems (9% vs 2%). Between 2015 and 2018, the proportion of patients with no/mild fibrosis (F0/F1) at first HCV treatment increased from 0% to 61%. Earlier treatment reduced the duration of infectiousness. Between 1 May 2017 and 1 May 2019, the proportion of chronic hepatitis C patients ever treated increased from 62% (198/321) to 80% (391/490). In parallel, the HCV-RNA prevalence among HCV antibody-positive patients declined from 36% (139/385) to 19% (113/593). The reinfection rate after successful treatment was 2.7/100 person-years. The number of HCV first diagnoses per year decreased from >20 up to 2015 to <10 in 2017 and 2018.

CONCLUSION

With nearly 100% DAA treatment success and a low reinfection rate, treatment uptake directly translates into a reduction of HCV-RNA prevalence. Eighty percent treatment uptake is feasible in OAT patients, and adherence and treatment success are not worse than in other populations. Duration of infectiousness and thus HCV transmission can be reduced by early detection and treatment of chronic hepatitis C.

摘要

背景

瑞士的丙型肝炎病毒 (HCV) 感染主要与静脉吸毒有关。自 2017 年以来,所有慢性丙型肝炎患者无论纤维化阶段如何,都可以用直接作用抗病毒药物 (DAA) 进行治疗。2019 年 3 月,联邦公共卫生办公室 (FOPH) 发布了针对吸毒者丙型肝炎管理的指南。为了在 2030 年实现丙型肝炎消除,需要 80%的患者接受治疗。

目的

为了评估在接受阿片类药物替代治疗 (OAT) 的患者中使用基于干扰素和无干扰素的 HCV 治疗的效果,并监测 HCV 的消除情况,联邦公共卫生办公室委托并由瑞士药物使用者医疗管理协会 (SAMMSU) 队列进行了一项为期两年的研究。

方法

自 2014 年以来,SAMMSU 队列从瑞士八个不同的中心招募 OAT 患者。除了每年进行随访外,还在 2017 年 5 月 1 日、2018 年 5 月 1 日和 2019 年 5 月 1 日这三个时间点收集横断面数据。分析了 HCV 治疗的接受率、依从性和成功率,以及再感染率、早期和晚期治疗的效果,以及“治疗即预防”方法的疗效。

结果

2017 年 5 月 1 日至 2019 年 5 月 1 日,SAMMSU 队列的患者人数从 623 人增加到 900 人:78%为男性,中位年龄为 45 岁,81%有过静脉吸毒史,13%为 HIV 阳性,66%为 HCV 抗体阳性。2012 年之前,HCV 治疗完全基于干扰素(每年最多 21 例患者),而自 2016 年以来完全基于无干扰素(2017 年有 102 例患者)。治疗成功率从 57%(112/198;基于干扰素)提高到 97%(261/268;基于无干扰素),无论是否存在肝硬化或之前对干扰素无反应。同时,在无干扰素时代,治疗变得更短,耐受性更好,导致提前停药(17%比 1%)和依从性问题(9%比 2%)减少。2015 年至 2018 年,首次 HCV 治疗时无/轻度纤维化(F0/F1)患者的比例从 0%增加到 61%。更早的治疗减少了传染性的持续时间。2017 年 5 月 1 日至 2019 年 5 月 1 日,慢性丙型肝炎患者接受治疗的比例从 62%(198/321)增加到 80%(391/490)。与此同时,HCV 抗体阳性患者中 HCV-RNA 的流行率从 36%(139/385)下降到 19%(113/593)。成功治疗后的再感染率为 2.7/100 人年。每年 HCV 首次诊断的数量从 2015 年的 >20 例减少到 2017 年和 2018 年的 <10 例。

结论

由于近 100%的 DAA 治疗成功率和低再感染率,治疗的接受率直接转化为 HCV-RNA 流行率的降低。在 OAT 患者中,80%的治疗接受率是可行的,并且依从性和治疗成功率并不比其他人群差。通过早期发现和治疗慢性丙型肝炎,可以减少传染性和丙型肝炎传播的持续时间。

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