DETERMINANTS OF HEPATITIS C & E MORBIDITY IN EGYPT

丙型肝炎的决定因素

• 批准号: 6802279
• 负责人: George Thomas Strickland
• 金额: $ 51.39万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802279
• 关键词: Egypt; clinical research; communicable disease transmission; cooperative study; epidemiology; hepatitis C; hepatitis C virus; human data; human morbidity; human pregnant subject; infectious hepatitis; virus antigen; virus infection mechanism

By using new molecular virological techniques, Non-A Non-B hepatitis patients have now been categorized into those infected with hepatitis C virus (HCV), a parenterally transmitted flavivirus, and hepatitis E virus (HEV), a fecal-oral transmitted "hepatitis E-like virus." WHO estimates that 170 million are infected with HCV, the most common cause of chronic viral hepatitis (CVH), post-necrotic cirrhosis of the liver and hepatocellular carcinoma (HCC). HEV is primarily transmitted in developing countries where it is the most common cause of acute viral hepatitis (AVH) and fulminating hepatitis, particularly in pregnant women. We and others have documented that the highest prevalence of HCV, and also possibly HEV, in the world occurs in Egypt. We have established a Network of Egyptians and Americans who are studying viral hepatitis and its cost to the country. In this ICIDR proposal, we will extend the work of this Network to include investigations of: (1) the effect that the host genome has on chronicity and cirrhosis following HCV infection (Project 1); (2) the host, viral, and environmental determinants of HCC and (because HCV is lymphotrophic as well as hepatotrophic) non-Hodgkins lymphoma (NHL, Project 2); and the epidemiology and complications of HEV (Project 3). Projects 1 & 2 will have case-control studies. The former will compare: (a) chronic carriers of HCV RNA vs. subjects who clear infection and (b) those with HCV who develop cirrhosis vs. those that show no signs of disease; while the latter compares HCC or NHL cases vs. age- and gender-matched controls. Projects 1-3 will have prospective cohort studies of 10,000 inhabitants of two villages with prevalence of anti-HCV of 9% and 24% and anti-HCV of 51 and 70%, respectively. Their goals will be to determine incidence of, and risk determinants for cirrhosis (Project 1), HCC and NHL (Project 2), and HEV infection and disease (Project 3). A cohort of pregnant women and children will be studied to assess HEV morbidity in pregnancy and exposures and disease in infancy. Domestic animals and peri-domestic rodents will be studied to determine whether HEV has a zoonotic component in Egypt. Viral genotypes, host class I and II alleles and candidate genes, e.g., chemokine receptors and HDL, a possible HCV receptor, and environmental exposures and their impact on host genes (p53 genetic fingerprinting) will be assayed. Because the scientific, administrative, logistic and laboratory network is in place and both HCV and HEV have such a high prevalence in Egypt, these investigations have a high probability of early success. Explanations for these very important questions can be obtained at a fraction of the cost and time as they could be found elsewhere, and the results should lead to the development of better interventions to prevent the two most important causes of liver disease in the world.

通过使用新的分子病毒学技术，非甲非乙型肝炎患者现已被分为感染丙型肝炎病毒（HCV）（一种肠胃外传播的黄病毒）和戊型肝炎病毒（HEV）（一种粪口传播的“戊型肝炎样病毒”）的患者。世界卫生组织估计，有 1.7 亿人感染丙型肝炎病毒，这是慢性病毒性肝炎 (CVH)、坏死后肝硬化和肝细胞癌 (HCC) 的最常见原因。 HEV 主要在发展中国家传播，是导致急性病毒性肝炎 (AVH) 和暴发性肝炎的最常见原因，特别是在孕妇中。我们和其他人已经证明，世界上 HCV（也可能是 HEV）患病率最高的地区是埃及。我们建立了一个由埃及人和美国人组成的网络，他们正在研究病毒性肝炎及其给国家造成的损失。在本 ICIDR 提案中，我们将扩展该网络的工作，包括以下方面的研究：(1) 宿主基因组对 HCV 感染后慢性病和肝硬化的影响（项目 1）； (2) HCC 和（因为 HCV 是淋巴营养性和肝营养性）非霍奇金淋巴瘤的宿主、病毒和环境决定因素（NHL，项目 2）； HEV 的流行病学和并发症（项目 3）。项目 1 和 2 将进行病例对照研究。前者将比较：(a) HCV RNA 慢性携带者与清除感染的受试者；(b) 患有肝硬化的 HCV 受试者与没有表现出疾病迹象的受试者；后者将 HCC 或 NHL 病例与年龄和性别匹配的对照进行比较。项目1-3将对两个村庄的10,000名居民进行前瞻性队列研究，这两个村庄的抗HCV患病率分别为9%和24%，抗HCV患病率分别为51%和70%。他们的目标是确定肝硬化（项目 1）、HCC 和 NHL（项目 2）以及 HEV 感染和疾病（项目 3）的发病率和风险决定因素。将研究一组孕妇和儿童，以评估怀孕期间的 HEV 发病率以及婴儿期的暴露和疾病。将研究家畜和近家畜啮齿动物，以确定戊型肝炎病毒在埃及是否具有人畜共患成分。将分析病毒基因型、宿主 I 类和 II 类等位基因以及候选基因，例如趋化因子受体和 HDL（一种可能的 HCV 受体）以及环境暴露及其对宿主基因的影响（p53 基因指纹）。由于科学、行政、后勤和实验室网络已经到位，而且丙型肝炎病毒和戊型肝炎病毒在埃及的流行率很高，因此这些调查早期成功的可能性很高。对这些非常重要的问题的解释只需花费在其他地方的一小部分成本和时间，并且结果应该会导致更好的干预措施的开发，以预防世界上肝病的两个最重要的原因。

项目成果

Hepatitis C virus-specific cell-mediated immune responses in children born to mothers infected with hepatitis C virus.

• DOI: 10.1016/j.jpeds.2012.06.057
• 发表时间: 2013-01
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: El-Kamary, Samer S.;Hashem, Mohamed;Saleh, Doaa A.;Abdelwahab, Sayed F.;Sobhy, Maha;Shebl, Fatma M.;Shardell, Michelle D.;Strickland, G. Thomas;Shata, Mohamed Tarek
• 通讯作者: Shata, Mohamed Tarek

A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.

• DOI: 10.1016/j.phymed.2009.02.002
• 发表时间: 2009-05
• 期刊: PHYTOMEDICINE
• 影响因子: 7.9
• 作者: El-Kamary, Samer S.;Shardell, Michelle D.;Abdel-Hamid, Mohamed;Ismail, Soheir;El-Ateek, Mohamed;Metwally, Mohamed;Mikhail, Nabiel;Hashem, Mohamed;Mousa, Amr;Aboul-Fotouh, Amr;El-Kassas, Mohamed;Esmat, Gamal;Strickland, G. Thomas
• 通讯作者: Strickland, G. Thomas

Changing patterns of acute viral hepatitis at a major urban referral center in Egypt.

埃及一个主要城市转诊中心的急性病毒性肝炎模式正在发生变化。

• DOI: 10.1086/511074
• 发表时间: 2007
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Zakaria,Soheir;Fouad,Rabab;Shaker,Olfat;Zaki,Sami;Hashem,Ahmed;El-Kamary,SamerS;Esmat,Gamal;Zakaria,Serag
• 通讯作者: Zakaria,Serag