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在尼泊尔,针对丙型肝炎病毒(HCV)单感染和 HIV-HCV 合并感染个体的 HCV 治疗。

Hepatitis C (HCV) therapy for HCV mono-infected and HIV-HCV co-infected individuals living in Nepal.

机构信息

National Academy of Medical Sciences, Kathmandu, Nepal.

Saint Joseph Mercy Ann Arbor Hospital, Ann Arbor, Michigan, United States of America.

出版信息

PLoS Negl Trop Dis. 2020 Dec 16;14(12):e0008931. doi: 10.1371/journal.pntd.0008931. eCollection 2020 Dec.

Abstract

BACKGROUND

Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting.

METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR.

CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

摘要

背景

尽管有直接作用抗病毒药物(DAA),但到 2030 年实现消灭病毒性肝炎的目标仍不太可能。在尼泊尔,一个专家联盟成立,通过尼泊尔地震灾后治疗丙型肝炎,为资源匮乏环境中扩大丙型肝炎治疗提供了一个模式。

方法/主要发现:2015 年,我们在尼泊尔的 4 个城市的 6 个阿片类药物替代治疗(OST)点建立了一个由肝病专家、实验室专家和社区领导组成的网络,对 838 名患者进行了治疗队列筛选,其中有 600 名患有丙型肝炎感染和既往或目前有药物使用史的患者。在第 1 阶段,患者接受了基于干扰素的方案治疗(n=46)。在第 2 阶段,对 135 名具有最佳预测因素(HIV 得到控制、无肝硬化、基线 HCV 病毒载量低)的患者采用了基于 DAA 的方案进行治疗。在第 3 阶段,无论 HCV 疾病严重程度、HIV 病毒血症或药物使用情况如何,均扩大了无干扰素 DAA 治疗。在第 12 周评估持续病毒学应答(SVR)。中位年龄为 37 岁,95.5%为男性。HCV 基因型为 3 型(53.2%)或 1a 型(40.7%),32%有肝硬化;42.5%为 HIV-HCV 合并感染。第 2 阶段和第 3 阶段的意向治疗(ITT)SVR 率分别为 97%和 81%。总体符合方案和 ITT 的 SVR 率分别为 97%和 85%。多变量分析显示,在加德满都治疗的患者有保护作用,物质使用和第 3 阶段治疗与未达到 SVR 相关。

结论/意义:无论患者的特征和疾病严重程度如何,在一个难以治疗的低收入人群中,都可能达到非常高的 SVR 率。在这项真实社区研究中观察到的优异治疗结果应促使尼泊尔进一步开展丙型肝炎治疗计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9eab/7773414/d0a3f102d018/pntd.0008931.g001.jpg

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