DETERMINANTS OF HEPATITIS C & E MORBIDITY IN EGYPT

通过使用新的分子病毒学技术，非甲非乙型肝炎患者现在已被分类为感染丙型肝炎病毒（HCV）（一种胃肠外传播的黄病毒）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。“世卫组织估计，有1.7亿人感染HCV，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）流行率最高的国家是埃及。我们已经建立了一个埃及人和美国人的网络，他们正在研究病毒性肝炎及其对国家的影响。在ICIDR的建议中，我们将扩展该网络的工作，包括以下研究：（1）宿主基因组对HCV感染后慢性和肝硬化的影响（项目1）;（2）HCC的宿主、病毒和环境决定因素，（因为HCV是嗜淋巴的以及嗜肝的）非霍奇金淋巴瘤（NHL，项目2）;以及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。前者比较：（a）HCV RNA慢性携带者与清除感染的受试者，和（B）发展为肝硬化的HCV患者与未显示疾病迹象的患者;而后者比较HCC或NHL病例与年龄和性别匹配的对照。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，抗-HCV流行率分别为9%和24%，抗-HCV流行率分别为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。将对一组孕妇和儿童进行研究，以评估妊娠期HEV发病率以及婴儿期暴露和疾病。将对家畜和围家养啮齿动物进行研究，以确定戊型肝炎病毒在埃及是否具有人畜共患病成分。病毒基因型、宿主I类和II类等位基因和候选基因，例如，将分析趋化因子受体和HDL（一种可能的HCV受体）以及环境暴露及其对宿主基因（p53遗传指纹）的影响。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，这些调查很有可能早日取得成功。这些非常重要的问题的解释可以在其他地方找到的成本和时间的一小部分获得，结果应该导致更好的干预措施的发展，以预防世界上两个最重要的肝病原因。

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.