Hepatitis C Core Antigen Testing: Still an Effective Diagnostic Method for Global Elimination of Hepatitis C.
Hepatitis C Core Antigen Testing: Still an Effective Diagnostic Method for Global Elimination of Hepatitis C.
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丙型肝炎核心抗原检测：仍然是全球消除丙型肝炎的有效诊断方法。
DOI：
10.1093/cid/ciz273
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kottilil,Shyam
中科院分区：
文献类型：
--
作者：
Mathur,Poonam;Kottilil,Shyam
慢性丙型肝炎感染影响全球7100万人，是导致肝功能衰竭和移植的最常见原因之一[1，2]。自从直接作用抗病毒药物(DAAs)问世以来，慢性丙型肝炎病毒(HCV)的管理已经发生了巨大的变化。DAA疗法的发展导致了全口服方案的高持续病毒学应答(SVR)率。与以前的注射干扰素方案相比，DAA的耐受性很好，后者耐受性较差，导致SVR率低于50%[3]。自2016年以来，庞格型DAA的发展为提供者治疗丙型肝炎患者创造了多样化的武器库。这些方案显示，无论种族、性别、基因、肝硬变或人类免疫缺陷病毒合并感染，SVR发生率均相同[4-7]。由于DAA的成功，世界卫生组织制定了到2030年全球消除病毒性肝炎的目标。这将部分通过将非专利DAA的生产外包给低收入和中等收入国家的制药公司来实现[8]。这些药物的成本也降低了[9]，从而成功地在全国范围内实施了消除计划。2013年，埃及的制造商将12周疗程的价格从美国的每名患者平均8.4万美元降至埃及的每名患者84美元。2013至2016年间，160万埃及人接受了丙型肝炎病毒治疗--超过了同期美国和欧洲接受治疗的所有患者的总和[10]。全球可获得性的改善和DAA成本的降低改变了丙型肝炎病毒的连续护理，因此重点放在开发护理点、高灵敏度、低成本的丙型肝炎病毒检测模式上。一个主要的重点是减少治疗期间频繁的实验室监测(包括病毒载量)，这在许多国家超过了DAA的成本。与用逆转录聚合酶链式反应(RT-PCR)检测丙型肝炎病毒RNA相比，丙型肝炎病毒核心抗原(Ag)检测是一种经济有效的确认丙型肝炎病毒感染的方法。据估计，90%的阳性丙型肝炎病毒RNA样本的RNA含量为10000IU/mL，属于丙型肝炎病毒核心抗原检测的敏感范围。在确定SVR时，丙型肝炎病毒抗原检测也被建议作为丙型肝炎病毒核糖核酸的替代品[11]。然而，人们对单独使用丙型肝炎病毒核心抗原提出了担忧，因为病毒载量非常低的患者，即病毒载量为3000 IU/毫升的患者，可能会出现假阴性的丙型肝炎病毒核心抗原检测结果，而这些患者在筛查过程中可能会被遗漏[12，13]。
Chronic hepatitis C infection affects 71 million people worldwide and is one of the most common causes of liver failure and transplantation [1, 2]. The management of chronic hepatitis C virus (HCV) has changed dramatically since the advent of direct-acting antivirals (DAAs). The development of DAA therapy resulted in all-oral regimens with high rates of sustained virologic response (SVR). Treatment with DAAs is well tolerated compared to previous regimens with injectable interferons that were poorly tolerated and resulted in SVR rates of less than 50%[3]. Since 2016, the development of pangenotypic DAAs has created a diverse arsenal for providers to treat patients with HCV. These regimens have demonstrated equal SVR rates regardless of race, gender, genotype, cirrhosis, or human immunodeficiency virus coinfection [4–7]. Due to the success of DAAs, the World Health Organization has established a goal for global elimination of viral hepatitis by 2030. This will be achieved, in part, by pharmaceutical companies that outsource manufacturing of generic DAAs to low-and middle-income countries [8]. The costs of these drugs have also been lowered [9], allowing for successful nationwide elimination programs to be implemented. In 2013, manufacturers in Egypt reduced the price of a 12-week course of treatment from an average cost of $84 000 per patient in the United States to $84 per patient in Egypt. Between 2013 and 2016, 1.6 million Egyptians received HCV treatment—more than all the patients treated in the United States and Europe combined during that period [10]. Improved accessibility and lowered costs of DAAs globally have shifted the HCV continuum of care so that the focus is on developing point-of-care, highly sensitive, low-cost HCV testing modalities. A major focus has been on reducing frequent laboratory monitoring (including viral load) during treatment, which surpasses the cost of DAAs in many countries. The HCV core antigen (Ag) test has been shown to be a cost-effective method for confirming HCV infection compared to the use of reversetranscription polymerase chain reaction (RT-PCR) for HCV RNA. It is estimated that 90% of the positive HCV RNA samples have an RNA> 10 000 IU/mL, which falls in the sensitivity range of HCV core Ag assays. The HCV Ag test has also been proposed as a substitute for HCV RNA in determining SVR [11]. However, concerns have been raised regarding the use of HCV core Ag alone since patients with a very low viral load (VLVL), that is, VL< 3000 IU/mL, may have a false-negative HCV core Ag test result, and these patients would be missed during screening [12, 13].