Biomarker and Analytical Core

Makerere大学和约翰斯·霍普金斯大学就乌干达的艾滋病毒和肝细胞癌(HCC)建立了一个合作伙伴关系：H2 U联盟。肝细胞癌在非洲是一种非常常见的致命癌症，随着艾滋病毒携带者寿命的延长，肝癌的负担将会增加。该联盟的首要目标是减轻撒哈拉以南非洲地区与艾滋病毒相关的肝癌的沉重负担。在长期合作的基础上，该联盟将扩大规模，回答有关艾滋病毒相关肝癌的基础流行病学和病因学的悬而未决的高度优先问题，同时扩大乌干达的临床和实验室研究能力，以解决这些问题。具体目标包括：1)提高乌干达研究人员对艾滋病毒相关肝癌进行高水平、协作、多学科科学调查的能力；2)巩固临床、人口和转化性研究基础设施；3)促进对艾滋病毒相关肝癌流行病学、机制和临床谱系的基础性了解；4)在资源有限的情况下，为适用于艾滋病毒相关肝癌的预防和治疗战略提供信息。我们提出了两个主要的临床项目，包括一项针对600例肝癌病例和600例对照的大型病例对照研究，以确定艾滋病毒和相关免疫抑制的作用。我们还将对3000名HIV感染的临床患者进行癌前肝硬变以及高危乙肝和黄曲霉毒素相关生物标志物的筛查，然后跟随这一高危人群进行定期的肝细胞癌筛查，以确定可行性以及是否可以识别早期肝细胞癌。我们的发展核心将实施H2 U学者奖，将一名乌干达调查员与一名霍普金斯大学的高级导师配对，并支持职业发展和一个合作试点项目。拟议的研究将加强我们对艾滋病毒相关肝癌的临床和机制的了解，为适当的治疗提供证据，并为在非洲抗击艾滋病毒和肝癌的干预战略提供信息。我们的综合研究和能力发展活动的影响将是建立H2 U联盟，作为非洲艾滋病毒和肝癌问题英才中心。

Proposed is a collaborative partnership between Makerere University and Johns Hopkins on HIV and hepatocellular carcinoma (HCC) in Uganda: The H2U Consortium. Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live longer, the HCC burden will increase. The overarching goal of the Consortium is to reduce the heavy burden of HIV-associated HCC in sub-Saharan Africa. Building on long-standing collaborations, the Consortium expands will answer unresolved, high priority questions on the fundamental epidemiology and etiology of HIV-associated HCC, while expanding the clinical and laboratory research capacity in Uganda to address these issues. The Specific Aims include: 1) To enhance Ugandan investigator capacity for conducting high-level, collaborative, multidisciplinary scientific investigation of HIV-associated HCC; 2) To solidify the clinical, population and translational research infrastructure; 3) To advance the foundational understanding of the epidemiology, mechanisms, and clinical spectrum of HIV-associated HCC; and 4)To inform prevention and treatment strategies applicable to HIV-associated HCC in resource-limited settings. We propose two major clinical projects, including a large case-control study of 600 HCC cases and 600 controls to define the role of HIV and related immunosuppression. We also will screen 3000 HIV-infected clinic patients for pre-malignant liver cirrhosis and for high-risk hepatitis B and aflatoxin-related biomarkers, then follow this high-risk group with regular HCC screening to determine feasibility and whether early stage HCC can be identified. Our Developmental Core will implement the H2U Scholars Award, pairing a Ugandan investigator with a senior Hopkins mentor and supporting career development and a collaborative pilot project. The proposed studies will enhance our clinical and mechanistic understanding of HIV-associated HCC, provide evidence on appropriate treatment, and inform intervention strategies to combat HIV and HCC in Africa. The impact of our integrated research and capacity development activities will be establishment of the H2U Consortium as a Center of Excellence on HIV and HCC in Africa.