Emerg Microbes Infect:台湾艾滋病毒携带者中丙型肝炎的微量消除

2022-08-07 从医路漫漫 MedSci原创

研究表明,DAA治疗可以实现非常高的持续病毒学应答率,并减少全因死亡率、肝脏相关并发症和肝细胞癌的发生。

背景:2016年6月,世界卫生组织(WHO)宣布了其首个全球目标,即到2030年消除病毒性肝炎这一主要公共卫生威胁,旨在将病毒性肝炎的新诊断病例减少90%,肝炎相关死亡病例减少65%。这项2016年减少丙型肝炎病毒(丙型肝炎病毒)传播的全球战略包括对捐献的血液产品进行筛查,针对注射吸毒者的减少危害计划(PWID),以及扩大获得直接作用抗病毒(DAA)治疗的机会。研究表明,DAA治疗可以实现非常高的持续病毒学应答率,并减少全因死亡率、肝脏相关并发症和肝细胞癌的发生。此外,从抗击艾滋病毒的“治疗即预防”战略中吸取教训,广泛使用DAA还可以降低社区中循环的丙型肝炎病毒水平,从而防止新的丙型肝炎病毒感染。在澳大利亚,在监狱人口中扩大DAA治疗的覆盖面后,发生的丙型肝炎病毒感染减少了近50%。埃及和格鲁吉亚的研究也表明,随着DAA治疗的扩大,普通人群中的丙型肝炎病毒感染显著减少。

然而,对许多国家来说,全国性的消除肝炎计划可能具有极大的挑战性和资源消耗。因此,与其寻求在整个人群中消除丙型肝炎病毒,从针对感染丙型肝炎病毒或发生丙型肝炎相关并发症的风险较高的特定亚群开始可能是合理的。这一“微消除”目标最常见的目标人群之一是艾滋病毒携带者(PLWH),因为许多流行病学研究表明,由于共同的行为风险因素,如共用针头/注射器和稀释性接触或无保护的性接触,丙型肝炎病毒合并感染率很高。此外,合并丙型肝炎病毒感染的慢性肝病患者进展为肝脏相关并发症的风险要高得多。

截至2022年1月,几个欧洲国家和澳大利亚报告了在PLWH中微量消除丙型肝炎病毒的进展。在瑞士的HIV队列研究中,在人群范围内进行丙型肝炎病毒筛查,然后不受限制地获得DAA治疗,导致丙型肝炎病毒发病率降低了78%。同样,在英国、澳大利亚和荷兰,针对男男性行为者(MSM)的PLWH的研究也表明,在实施不受限制的早期DAA治疗后,丙型肝炎发病率降低了49%-71%。瑞士的研究也证明了在PLWH中实施微量消除计划后,丙型肝炎病毒控制的持续效果。在亚太地区,也有一些惩教机构或监狱中的丙型肝炎病毒微量消除方案。然而,考虑到亚太地区丙型肝炎病毒感染的较高流行率和发病率,考察在亚太地区推出DAA后丙型肝炎病毒微消除进展的研究仍然很少。

目的:在这项为期10年的队列研究中,我们的目的是调查在实施DAA治疗计划前后台湾地区PLWH中的丙型肝炎病毒血症的趋势。

方法:在2011年1月至2021年12月期间在台湾一家指定为HIV护理的大型医院寻求护理的PLWH被追溯纳入其中。对于研究期间丙型肝炎病毒血清阳性或丙型肝炎病毒血清转换的PLWH,使用存档样本进行系列HCVRNA检测,以确认丙型肝炎病毒血症的存在,并估计丙型肝炎病毒血症的患病率和发病率。

结果:总体而言,4199名妇幼保健员参与了总计27,258.75人年的后续行动(PYFU)。随着DAA报销和治疗可获得性的改善,丙型肝炎病毒血症的患病率从2018年的峰值6.21%(95%CI,5.39-7.12%)下降到2021年的2.09%(95%CI,1.60-2.77%)(下降66.4%[95%CI,55.4-74.7%]);发病率从2019年的25.94/1000 PYFU(95%CI,20.44-32.47)下降到12.15%/1000 PYFU(95%CI,8.14-17.44)(下降53.2%[95%CI,27.3-70.6%])。然而,丙型肝炎病毒再感染的比例继续增加,占2021年发生的丙型肝炎病毒感染的82.8%。

图1在每个日历年的随访中,跟踪的艾滋病毒携带者(PLWH)的人数、进行的丙型肝炎病毒RNA检测的数量和观察到的年度辍学率。辍学被定义为在上一个日历年被包括在内,但没有可用于丙型肝炎病毒抗体或RNA检测的数据或样本的PLWH。

图2.2011-2021年艾滋病毒携带者中丙型肝炎病毒血症发病率和流行率的演变。PYFU,人-年的随访。

图3.2011-2021年期间发生的丙型肝炎病毒血症病例和丙型肝炎病毒再感染的比例。

结论:我们观察到,随着台湾DAA治疗计划的扩大,PLWH中的丙型肝炎病毒血症显著下降。有必要进一步改善获得DAA再治疗的机会,以实现微消除丙型肝炎病毒的目标。

原文出处:Chen GJ,  Ho SY,  Su LH,et al.Hepatitis C microelimination among people living with HIV in Taiwan.Emerg Microbes Infect 2022 Dec;11(1)

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    2023-07-20 qblt
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