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: 10689163
• 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/10689163
• 关键词: AFP gene; Acceleration; Advocate; Africa; Africa South of the Sahara; African; Age; Albumins; Antigens; Attenuated; Behavioral; Biological Markers; Birth; CD4 Lymphocyte Count; Cancer Etiology; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Research; Country; Data; Development; Diagnostic; Dose; Eligibility Determination; Etiology; Fibrosis; Foundations; Funding; Genotype; Goals; Guidelines; HIV; HIV Infections; Hepatitis B Infection; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B Virus; Hepatitis B e Antigens; Hepatitis C virus; Human; Image; Incidence; Individual; Infection; 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; RNA; 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; Universities; Viral; Virus Diseases; Virus Replication; Visit; alpha-Fetoproteins; antiretroviral therapy; cell injury; chronic infection; co-infection; cohort; data quality; design; dosimetry; elastography; high risk; high risk population; insight; novel; novel marker; recruit; response; screening; sociodemographics; study population; treatment as prevention; treatment response; ultrasound; 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）是一种非常常见和致命的癌症在非洲，并与艾滋病毒感染者的生活 时间越长，HCC的负担可能会增加。在先前的研究中，我们的团队确定了慢性B型肝炎感染 C病毒（HBV、HCV）、HIV和曼氏血吸虫是HCC的独立危险因素。相比 对于美国，撒哈拉以南非洲的HCC发生在更年轻和更晚期的阶段， 个月建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、塞内加尔的法恩大学和约翰霍普金斯大学专注于艾滋病毒和肝细胞癌 非洲的肝癌（HCC）：H2 A联盟。建立在长期的合作研究，指导 在这两个国家的临床活动，我们的总体目标是减少肝癌的沉重负担， 撒哈拉非洲。我们提倡使用适当的药物治疗来研究癌症拦截策略 以中断或逆转这些导致HCC的感染的影响。联合会的活动旨在 加强临床、人口和转化研究基础设施， 调查人员有能力对艾滋病毒、慢性感染和肝细胞癌进行高级别的合作调查。在 在本项目中，我们将建立一个大型的HBV和HBV/HIV合并感染者的前瞻性队列， 从乌干达和塞内加尔招募。针对HBV的指南适当的抗病毒治疗将 启动和HCC监测超声和甲胎蛋白进行。基线和6个月研究 访视将收集问卷调查、临床、超声和弹性成像数据。我们将定义临床结果， 在降低标准和新型病毒生物标志物、肝脏稳定和消退方面的HBV治疗 纤维化，并降低HCC的发病率。同时，使用一种新的白蛋白内收体切除术方法，我们将 研究氧化应激途径的变化并鉴定与HBV和HIV相关的新生物标志物 感染.对于这些分析中的每一项，将HIV合并感染作为关键效应修饰因子进行评价。的影响 这些研究将为治疗和筛查方法提供信息，并可能发现新的生物标志物。 用于指导HBV管理和HCC预防。