Active Viral Hepatitis Diagnostics to Support Prevention/Treatment of HCC

描述（由申请人提供）：支持预防/治疗HCC的主动病毒性肝炎诊断由于慢性B型肝炎（HBV）和丙型肝炎（HCV）病毒感染的高度流行，肝细胞癌（HCC）在撒哈拉以南非洲非常常见。目前，撒哈拉以南非洲的患者通常处于疾病晚期，预期寿命仅为3个月。早期诊断可以通过两种方式降低HCC死亡率：1）HBV或HCV患者的分期更早，肿瘤（如果存在）更小，因此更容易用酒精消融治疗，这是该地区目前的护理标准; 2） 早期发现的慢性HBV或HCV患者可以用直接作用的抗病毒药物（DAA）治疗，从而降低发病率，包括减少HCC。本申请的目标是开发低成本的床旁诊断测试，以检测和监测活动性HBV和/或HCV感染的治疗。首先要开发的检测将是HCV核心抗原定性检测，以识别活动性HCV感染患者。该检测将移植到与西北全球健康基金会（NGHF）合作开发的LYNX免疫分析平台上。为快速诊断婴儿HIV感染的LYNX p24抗原快速侧向流检测试剂盒开发的检测条件将进行调整，以解决高度相似的问题：检测血浆中的HCV核心抗原病毒标志物。第二项检测将是多重HBV/HCV病毒载量测定，以确定何时开始治疗并监测DAA治疗的病毒应答。该分析将被移植到Savanna集成核酸提取、扩增和检测系统上，该系统目前正在与Quidel Corporation和NGHF合作开发。为Savanna RealTime HIV-1 Assay（R）开发的检测条件将用于HBV/HCV病毒载量测定。LYNX和Savanna平台都是为有限资源环境而设计的。它们价格低廉，易于操作，坚固耐用。所有试剂均随检测试剂盒提供，无需冷藏。这些检测试剂盒的分析和临床性能将在乔斯大学教学医院（乔斯，尼日利亚）的实验室和临床验证研究中得到证明。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。病毒性肝炎的早期检测和改善监测的影响将促进早期治疗，从而预防癌症发生和/或早期诊断，改善中低收入国家患者的结局。

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.