Antiviral treatment as prevention for HBV- and HBV/HIV-associated hepatocellular carcinoma

抗病毒治疗预防 HBV 和 HBV/HIV 相关肝细胞癌

• 批准号: 10259886
• 负责人: Gregory D Kirk
• 金额: $ 27.03万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10259886
• 关键词: AFP gene; Advocate; Africa; Africa South of the Sahara; African; Age; Albumins; Antigens; Antiviral Agents; Attenuated; Behavioral; Biological Markers; Birth; CD4 Lymphocyte Count; Cancer Etiology; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Data; Clinical Research; Country; Data; Development; Diagnostic; Dose; Eligibility Determination; Etiology; Fibrosis; Foundations; Funding; Genotype; Goals; Guidelines; HIV; HIV Infections; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Virus; Hepatitis B e Antigens; Hepatitis C virus; Human; Image; Incidence; Individual; Infection; Intercept; Interruption; Interview; Investigation; Liver Fibrosis; Malignant Neoplasms; Medical; Mentors; Monitor; Mutation; Outcome; Oxidative Stress; Oxidative Stress Pathway; Participant; Pathogenesis; Pathology; Patients; Persons; Population; Population Attributable Risks; Population Research; Prevention; Preventive vaccine; Primary carcinoma of the liver cells; Process; Prospective cohort; Questionnaires; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Sampling; Schistosoma mansonii infection; Senegal; Serum; Serum Albumin; Standardization; Tenofovir; Testing; Translational Research; Treatment Protocols; Uganda; Ultrasonography; Universities; Viral; Virus Diseases; Virus Replication; Visit; alpha-Fetoproteins; antiretroviral therapy; cell injury; chronic infection; co-infection; cohort; data quality; design; dosimetry; elastography; genomic RNA; high risk; insight; novel; novel marker; recruit; response; screening; sociodemographics; study population; treatment as prevention; treatment response; vaccine acceptance; viral DNA; virus core

Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live longer, the HCC burden may increase. In prior studies, our team identified chronic infection with hepatitis B and C viruses (HBV, HCV), HIV and Schistosomiasis mansoni as independent risk factors for HCC. Compared to the US, HCC in sub-Saharan Africa occurs at younger age and more advanced stage with survival of only months. Proposed is an East and West African partnership between colleagues at Makerere University in Uganda, Fann University in Senegal and Johns Hopkins University focused on HIV and hepatocellular carcinoma (HCC) in Africa: The H2A Consortium. Building on long-standing collaborative research, mentoring and clinical activities in both countries, our overarching goal is to reduce the heavy burden of HCC in sub- Saharan Africa. We advocate investigating cancer interception strategies using appropriate medical treatments to interrupt or reverse the impact of these HCC-causing infections. Consortium activities are designed to enhance both the clinical, population and translational research infrastructure and individual African investigator capacity to conduct high-level, collaborative investigation of HIV, chronic infections and HCC. In this project, we will form a large, prospective cohort of HBV and HBV/HIV co-infected persons with balanced recruitment from both Uganda and Senegal. Guideline-appropriate antiviral treatment against HBV will be initiated and HCC surveillance with ultrasound and alpha-fetoprotein performed. Baseline and six-month study visits will collect questionnaire, clinical, ultrasound, and elastography data. We will define clinical outcomes of HBV treatment in terms of reduced standard and novel viral biomarkers, stabilization and regression of liver fibrosis, and reduced incidence of HCC. In parallel, using a novel albumin adductomics approach, we will investigate changes in oxidative stress pathways and identify novel biomarkers relevant for both HBV and HIV infections. For each of these analyses, HIV co-infection is evaluated as a key effect modifier. The impact of these studies will be to inform treatment and screening approaches and potentially identify novel biomarkers for guiding HBV management and HCC prevention.

肝细胞癌 (HCC) 是非洲一种非常常见且致命的癌症，随着艾滋病毒患者的生存 时间越长，HCC 负担可能会增加。在之前的研究中，我们的团队发现了乙型肝炎的慢性感染 C 病毒（HBV、HCV）、HIV 和曼氏血吸虫病是 HCC 的独立危险因素。比较的 与美国相比，撒哈拉以南非洲地区的 HCC 发生年龄更小，阶段更晚期，生存期仅为 几个月。提议在马凯雷雷大学的同事之间建立东非和西非伙伴关系 乌干达、塞内加尔范恩大学和约翰霍普金斯大学专注于艾滋病毒和肝细胞 非洲癌症 (HCC)：H2A 联盟。建立在长期合作研究、指导的基础上 以及两国的临床活动，我们的总体目标是减轻亚裔 HCC 的沉重负担 撒哈拉非洲。我们主张使用适当的医疗方法研究癌症拦截策略 中断或扭转这些引起 HCC 的感染的影响。联盟活动旨在 加强临床、人口和转化研究基础设施以及非洲个体 研究人员对艾滋病毒、慢性感染和肝癌进行高水平协作调查的能力。在 在这个项目中，我们将形成一个大型的、前瞻性的 HBV 和 HBV/HIV 共同感染者队列，其平衡情况如下： 来自乌干达和塞内加尔的招募。适合指南的针对 HBV 的抗病毒治疗将 启动并使用超声和甲胎蛋白进行 HCC 监测。基线和六个月研究 访问将收集问卷、临床、超声和弹性成像数据。我们将定义临床结果 乙肝治疗包括降低标准和新型病毒生物标志物、肝脏的稳定和消退 纤维化，并降低 HCC 的发病率。同时，使用一种新颖的白蛋白加合组学方法，我们将 研究氧化应激途径的变化并确定与 HBV 和 HIV 相关的新型生物标志物 感染。对于每项分析，HIV 合并感染都被评估为关键效应调节因素。的影响 这些研究将为治疗和筛查方法提供信息，并有可能识别新的生物标志物 指导 HBV 管理和 HCC 预防。