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

肝细胞癌在非洲是一种非常常见和致命的癌症，作为艾滋病毒携带者的患者生活在非洲。 时间长了，肝细胞癌的负担可能会增加。在之前的研究中，我们的团队确认了慢性乙肝感染 C病毒(乙肝病毒、丙型肝炎病毒)、HIV和曼氏血吸虫病(Sm)是肝细胞癌的独立危险因素。 与美国相比，撒哈拉以南非洲地区的肝癌发生年龄更小，晚期更严重， 只存活了几个月。Makerere的同事们提议在东非和西非建立伙伴关系 乌干达大学、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 非洲的肝细胞癌：H2 A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 撒哈拉以南非洲的肝细胞癌。我们主张研究癌症拦截策略，使用适当的 中断或逆转引起肝细胞癌感染的影响的医疗治疗。要了解我们的数据 展示慢性乙肝和Sm感染之间的协同作用，我们将研究乙肝的临床 以及外周和肝脏对吡喹酮治疗的免疫学反应。 随着时间的推移，肝脏Sm相关炎症从Th1偏向Th2转变，我们假设这种转变 可能促进乙肝病毒的复制。我们将评估Sm治疗和治疗过程中血浆HBVDNA的动态变化 将这些与血浆细胞因子的同期变化联系起来，以表征Th1移位的炎症。 我们还同时检测了乙肝病毒特异性的CD4和CD8T细胞反应，以及Sm治疗的措施 功效。通过对丹参治疗前后以及肝细胞癌患者的肝活检的调查， 我们期望在人类身上证实Sm是致癌的，并且Sm治疗只会部分减少 致癌基因的表达。艾滋病毒将作为每种关系的修饰符进行评估。鉴于我们的 强劲的记录，拟议的研究很有可能成功地为减轻负担做出贡献 以及提高对非洲慢性感染和肝癌的了解。

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.