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: 10084615
• 负责人: Gregory D Kirk
• 金额: $ 33.25万
• 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/10084615
• 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; Vaccination; 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 response; uptake; 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）是非洲非常普遍且致命的癌症，随着HIV患者的活力 更长的时间，HCC负担可能会增加。在先前的研究中，我们的团队确定了乙型肝炎的慢性感染 和C病毒（HBV，HCV），HIV和血吸虫病Mansoni作为HCC的独立危险因素。比较的 对于美国，撒哈拉以南非洲的HCC发生在年轻时，而更高级的阶段仅生存 月份。拟议的是Makerere University的同事之间的东非和西非伙伴关系 乌干达，塞内加尔的范恩大学和约翰·霍普金斯大学专注于艾滋病毒和肝细胞 非洲癌（HCC）：H2A财团。在长期合作研究的基础上进行指导 在两国的临床活动中，我们的总体目标是减轻hcc的沉重负担 撒哈拉非洲。我们主张使用适当的医疗治疗调查癌症截获策略 中断或扭转这些引起HCC引起的感染的影响。财团活动旨在 增强临床，人口和转化研究基础设施和单个非洲人 研究者对艾滋病毒，慢性感染和HCC进行高级，合作研究的能力。在 这个项目，我们将组建一个大型的，预期的HBV和HBV/HIV共同感染者 乌干达和塞内加尔的招募。针对HBV的适用于指南的抗病毒治疗将是 进行超声和α-胜蛋白的启动和HCC监视。基线和六个月的研究 访问将收集问卷，临床，超声和弹性图数据。我们将定义 HBV处理标准和新型病毒生物标志物，肝脏的稳定和消退 纤维化和HCC发病率降低。同时，使用一种新颖的白蛋白加成学方法，我们将 研究氧化应激途径的变化，并鉴定与HBV和HIV相关的新型生物标志物 感染。对于这些分析中的每一个，将HIV共感染评估为关键效应修饰符。的影响 这些研究将为治疗和筛查方法提供信息，并有可能识别新型的生物标志物 用于指导HBV管理和HCC预防。