Active Viral Hepatitis Diagnostics to Support Prevention/Treatment of HCC

描述(由申请人提供)：主动病毒性肝炎诊断支持预防/治疗肝细胞癌(肝细胞癌)在撒哈拉以南非洲地区非常常见，因为慢性乙肝(乙肝)和丙型肝炎(丙型肝炎)病毒感染非常普遍。目前，撒哈拉以南非洲的患者通常处于晚期疾病，预期寿命只有三个月。早期诊断可以通过两种方式降低肝癌死亡率：1)携带乙肝病毒或丙型肝炎病毒的患者分期更早，如果存在肿瘤，肿瘤会更小，因此更容易通过酒精消融治疗，这是该地区目前的治疗标准；以及2) 早期确诊为慢性乙肝或丙型肝炎的患者可以使用直接作用的抗病毒药物(DAA)进行治疗，从而减少发病率，包括较少的肝癌。该应用程序的目标是开发低成本的护理点诊断测试，以检测和监测活动性乙肝病毒和/或丙型肝炎病毒感染的治疗。将开发的第一个测试将是丙型肝炎病毒核心抗原定性测试，以识别活动性丙型肝炎病毒感染的患者。这项检测将被移植到与西北全球健康基金会(NGHF)合作开发的THLynx免疫检测平台上。为Lynx p24抗原快速侧向流动分析开发的快速诊断婴儿艾滋病毒感染的测试条件将被调整，以解决一个高度相似的问题：从血浆中检测丙型肝炎病毒核心抗原病毒标志物。第二个测试将是多重的乙肝病毒/丙型肝炎病毒载量分析，以确定何时开始治疗并监测对DAA治疗的病毒反应。这项分析将被移植到萨凡纳综合核酸提取、扩增和检测系统上，该系统目前正在与Quidel公司和NGHF合作开发。为萨凡纳实时HIV-1检测(注册商标)开发的测试条件将用于乙肝病毒/丙型肝炎病毒载量检测。Lynx和Savanna平台都是为在有限的资源环境中使用而设计的。它们价格低廉，易于操作，而且坚固耐用。所有试剂都配有检测试剂盒，不需要冷藏。这些检测的分析和临床性能将在尼日利亚乔斯的乔斯大学教学医院的实验室和临床验证研究中得到验证。这些测试将被转移到各自的制造商，并将寻求监管部门的批准。更早发现和改进对病毒性肝炎的监测的影响将促使更早的治疗，从而预防癌症的发生和/或早期诊断，从而改善低收入和中等收入国家患者的结果。

DESCRIPTION (provided by applicant): Active Viral Hepatitis Diagnostics to Support Prevention/Treatment of HCC Hepatocellular carcinoma (HCC) is very common in sub-Saharan Africa due to highly prevalent chronic hepatitis B (HBV) and hepatitis C (HCV) viral infection. Currently, patients in sub-Saharan Africa typically present in late stage disease, having a life expectancy of just three months. Earlier diagnosis could reduce HCC mortality in two ways: 1) patients with HBV or HCV would be staged earlier and tumors, if present, would be smaller and therefore easier to treat with alcohol ablation, the current standard of care in the region; and 2) patients identified earlier with chronic HBV or HCV could be treated with direct acting antiviral agents (DAAs) leading to reduced morbidity including less HCC. The goal of this application is to develop low cost point-of-care diagnostic tests to detect and monitor the treatment of active HBV and/or HCV infections. The first test to be developed will be an HCV core antigen qualitative test to identify patients with an active HCV infection. This assay will be ported on th LYNX immunoassay platform developed in collaboration with the Northwestern Global Health Foundation (NGHF). The test conditions developed for the LYNX p24 Antigen Rapid Lateral Flow Assay for Rapid Diagnosis of HIV Infection in Infants will be adapted to address a highly analogous problem: the detection of the HCV core antigen viral marker from plasma. The second test will be a multiplexed HBV/HCV viral load assay to determine when to initiate therapy and to monitor the viral response to DAA treatment. This assay will be ported onto the Savanna integrated nucleic acid extraction, amplification & detection system that is currently being developed in collaboration with the Quidel Corporation and NGHF. The test conditions developed for the Savanna RealTime HIV-1 Assay(R) will be used for the HBV/HCV viral load assay. Both the LYNX and the Savanna platforms have been designed for use in limited resource settings. They are inexpensive, easy to operate and robust. All reagents are provided with the test kits and no refrigeration is required. The analytical and clinical performance of these assays will be demonstrated in both laboratory and clinical validation studies at the Jos University Teaching Hospital in Jos, Nigeria. The tests will be transferred to their respective manufacturers, and regulatory approval for will be sought. The impact of earlier detection and improved monitoring of viral hepatitis will prompt earlier treatment resulting in prevention of carcinogenesis and/or earlier stage diagnosis with improved outcomes in patients in low and middle income countries.