Background

Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia.

Methods

The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing.

Findings

Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31–55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy.

Interpretation

This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection.

Funding

Médecins Sans Frontières.

中文翻译：

---

柬埔寨农村地区的丙型肝炎去中心化检测和治疗：评估整合到现有公共卫生系统中的简化服务模式

背景

丙型肝炎病毒（HCV）的直接作用抗病毒治疗为非专业临床人员在分散环境中提供简化的护理模式提供了机会。但是，在低收入和中等收入国家，增加获得HCV护理的总体机会仍然是一个持续的问题，特别是对于城市中心以外的人群。因此，我们的目标是在柬埔寨马德望省的农村卫生业务区内，通过分散卫生服务实施HCV护理的简化模型。

方法

该研究队列包括Moung Russei卫生业务区的成年居民（≥18岁），他们在13个当地卫生中心自愿接受了筛查。血清学测试通过快速诊断测试使用SD Bioline HCV（SD Bioline HCV，Standard Diagnostics，韩国）和毛细血管血进行。HCV病毒载量测试由GeneXpert（美国加利福尼亚州桑尼维尔市的Cepheid）进行。病毒血症患者（HCV病毒载量≥10IU / mL）接受了普通医师的治疗前评估，并在卫生操作区转诊医院接受了最低限度治疗评估测试。没有其他并发症的病毒血症患者在当地医疗中心接受了护理人员提供的所有HCV护理随访，由肝硬化代偿失调的患者接受过直接作用的抗病毒HBV合并感染治疗，或其他需要观察的合并症，在转诊医院继续接受普通医生的护理。被认为有资格接受治疗的患者需口服索非布韦（400 mg）和达卡他韦（60 mg）口服，连续12周，或者对于失代偿性肝硬化患者或以前接受过直接作用抗病毒药物的患者，每天口服24周。HCV治愈定义为治疗后12周持续的病毒学应答（HCV病毒载量<10 IU / mL）。在治疗开始至治疗后12周之间的任何时间评估患者的严重和非严重不良事件。对于失代偿性肝硬化患者或先前用直接作用抗病毒药治疗的患者，则为24周。HCV治愈定义为治疗后12周持续的病毒学应答（HCV病毒载量<10 IU / mL）。在治疗开始至治疗后12周之间的任何时间评估患者的严重和非严重不良事件。对于失代偿性肝硬化患者或先前用直接作用抗病毒药治疗的患者，则为24周。HCV治愈定义为治疗后12周持续的病毒学应答（HCV病毒载量<10 IU / mL）。在治疗开始至治疗后12周之间的任何时间评估患者的严重和非严重不良事件。

发现

在2018年3月12日至2019年1月18日之间，对10 425名居民（即在蒙苏西医疗卫生区估计的136 571名成年人中的7·6％）进行了筛查。在接受筛查的这些患者中，中位年龄为44岁（IQR 31-55），其中HCV抗体阳性为778（7·5％）。778例抗体阳性患者中的761例（97·8％）进行了HCV病毒载量测试，其中540例（71·0％）进行了HCV病毒学检测。在这540例患者中，与治疗和后续护理的联系很高，其中533例（98·7％）在HCV诊所接受了基线咨询，其中530例（99·4％）开始了治疗。开始治疗的530例患者中有485例（91·5％）在健康中心接受了随访，转诊医院随访了45例（8·5％）。在开始直接作用抗病毒治疗的530例患者中，有515例（97·2％）完成了治疗。随后，515名患者中的466名（90·5％）完成了随访，而466名患者中的459名（98·5％）在治疗后12周实现了持续的病毒学应答。两次（0·4％）不良事件（疲劳[n = 1]和胃部不适[n = 1]）和五次（0·9％）严重不良事件（感染[n = 2]，心血管疾病[n = 1] ]和恐慌发作[n = 1]，据报道在开始治疗的患者中缺少导致严重不良事件的原因之一的数据。所有严重不良事件均被认为与治疗无关。并报告了开始治疗的患者中缺少导致严重不良事件的原因之一的数据。所有严重不良事件均被认为与治疗无关。并报告了开始治疗的患者中缺少导致严重不良事件的原因之一的数据。所有严重不良事件均被认为与治疗无关。

解释

该试点项目表明，高度简化，分散的HCV护理模式可以整合到低收入或中等收入国家的农村公共卫生系统中，同时保持较高的患者保留率，治疗效果和安全性。该项目通过非专业人员的临床工作人员通过可访问的，分散的初级保健中心提供护理，从而提高了有限资源的有效利用，并最大程度地发挥了检测和治疗HCV感染者的潜力。

资金

无国界医生组织。