Interaction of Schistosomiasis mansoni and hepatitis B virus infections on hepatocellular carcinoma

曼氏血吸虫病和乙型肝炎病毒感染对肝细胞癌的相互作用

• 批准号: 10084616
• 负责人: David L Thomas
• 金额: $ 28.27万
• 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/10084616
• 关键词: Advocate; Affect; Africa; Africa South of the Sahara; African; Aftercare; Age; Animal Model; Antigens; Blood Circulation; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cancer Etiology; Chronic; Chronic Care; Chronic Hepatitis B; Clinical; Collaborations; Country; DNA Double Strand Break; Data; Eligibility Determination; Genes; Genetic; Goals; HBV Genotype; HIV; HIV Infections; Hepatic; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Virus; Hepatitis C virus; Hepatocyte; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Immune response; Immunity; Immunologics; Immunology; In Vitro; Income; Infection; Inflammation; Inflammatory; Intercept; Interruption; Investigation; JUN gene; Light; Liver; Malignant Neoplasms; Measures; Medical; Mentors; Mesentery; Oncogenes; Oncogenic; Pathway interactions; Patients; Persons; Physiological; Plasma; Praziquantel; Primary carcinoma of the liver cells; Proto-Oncogenes; Public Health; Research; Residual state; Risk; Risk Factors; Schistosoma mansoni; Schistosoma mansonii infection; Senegal; Site; System; T cell response; Testing; Time; Tissues; Treatment Efficacy; Uganda; Universities; Venous; Virus Diseases; Virus Replication; carcinogenicity; chronic infection; cytokine; egg; improved; inflammatory milieu; insight; liver biopsy; macrophage; mortality; novel; response; standard of care; viral DNA

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 (Sm) 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 HCC-causing infections. To understand our data demonstrating synergistic interaction between chronic HBV and Sm infections, we will examine HBV clinical and immunological responses in the periphery and the liver in response to Sm treatment with praziquantel. Over time, liver Sm-related inflammation transitions from a Th1 to Th2 bias, and we hypothesize this transition may promote HBV replication. We will evaluate the dynamics of plasma HBV DNA during Sm treatment and correlate these with contemporaneous changes in plasma cytokines to characterize Th1 shifted inflammation. We also concurrently examine HBV specific CD4+ and CD8+ T cell responses, and measures of Sm treatment efficacy. Through investigation of liver biopsies on patients before and after SM treatment as well as with HCC, we anticipate confirming in humans that Sm is pro-carcinogenic and that Sm treatment only partially diminishes expression of pro-carcinogenic genes. HIV will be evaluated as a modifier of each relationship. Given our strong record, the proposed research has a high likelihood for successful contribution to reducing the burden and improving understanding of chronic infections and HCC in Africa.

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（Sm）是HCC的独立危险因素。 与美国相比，撒哈拉以南非洲的HCC发生在更年轻的年龄和更晚期的阶段， 仅存活数月。建议在Makerere的同事之间建立东非和西非伙伴关系 乌干达大学、塞内加尔法恩大学和约翰霍普金斯大学重点研究艾滋病毒和 非洲的肝细胞癌（HCC）：H2A联盟。建立在长期合作的基础上 在两国的研究、指导和临床活动中，我们的首要目标是减轻沉重的负担， 撒哈拉以南非洲的HCC。我们提倡研究癌症拦截策略，使用适当的 医学治疗以中断或逆转HCC引起的感染的影响。了解我们的数据 证明慢性HBV和Sm感染之间的协同作用，我们将研究HBV临床 外周和肝脏对吡喹酮治疗的免疫反应。 随着时间的推移，Sm相关的肝脏炎症从Th1向Th2偏倚转变，我们假设这种转变 可能促进HBV复制。我们将评估Sm治疗期间血浆HBV DNA的动态变化， 将这些与血浆细胞因子的同时变化相关联，以表征Th1转移的炎症。 我们还同时检查了HBV特异性CD4+和CD8+ T细胞反应，以及Sm治疗的措施。 功效通过对SM治疗前后以及HCC患者的肝活检进行调查， 我们预计在人类中证实Sm是促癌的，Sm治疗只能部分减少 促癌基因的表达。艾滋病毒将作为每种关系的修饰因子进行评估。鉴于我们 良好的记录，拟议的研究有很大的可能性，成功的贡献，以减少负担 提高对非洲慢性感染和HCC的认识。