REPLICATION OF HEPATITIS B VIRUS AND THE RISK OF LIVER CANCER

慢性感染乙肝病毒是主要的危险因素 对于原发性肝细胞癌，占80%的病例 全世界。40%的男性慢性乙肝携带者最终将死亡 另有15%的人预计会死于肝硬变。这种风险是 分布不均，但对与哪种病毒相关的了解甚少 相关因素与PHC的发病风险相关。 在项目I，预防原发性肝癌中，共有5,000人参加 慢性携带者正在从东亚移民中招募， 特拉华河谷的难民人口。项目I的目标是 应用甲胎蛋白在可治疗的早期阶段检测PHCS 监控。项目II的目标是检验以下假设 乙肝病毒的持续复制与增加的风险有关 发展为慢性肝病和原发性肝癌。 这一假设将通过对单独收集的血清进行检测来验证 已知与复制HBs Ag和HBs相关的乙肝标志物的样本 HBVDNA，以及一些最近发现的可能是 与复制直接或反向关联。其中包括HB PRE- S1，Hb Pre-S2，抗Poll(抗DNA聚合酶)，抗Pre-S1，抗Pre-S2， HBxAg和抗HBx。项目I收集的数据包括年龄、性别、 临床、生化和行为信息将被用作 此项目中的协变量。将分析各种因素之间的关系 到彼此，到乙肝病毒复制，到慢性肝病，以及他们的 患原发性肝癌的风险。将使用单变量和多变量分析来 确定影响最高的个人和因素组合 风险。 识别与病毒相关的风险因素可能允许更深层次的 对慢性肝病和肝癌发病机制的认识。 识别最高风险的个人将识别那些 从治疗性和预防性中受益最多的人 干预策略。理想情况下，病毒风险因素的知识可以 导致了预防严重肝病方法的发展 永远不会发生。

Chronic infection with hepatitis B virus (HBV) is the major risk factor for primary hepatocellular carcinoma, accounting for 80% of the cases worldwide. Forty percent of male chronic HBV carriers will eventually die of PHC and another 15% are projected to die of cirrhosis. This risk is unevenly distributed, but little is known about which virus related factors are associated with risk of PHC. In Project I, Prevention of Primary Liver Cancer, a cohort of 5,000 chronic carriers is being recruited from the East Asian immigrant and refugee population of the Delaware Valley. The objective of Project I is to detect PHCs at an early treatable stage using alpha fetoprotein monitoring. The objective of Project II is to test the hypothesis that persistent replication of HBV is associated with an increased risk of developing chronic Liver disease and PHC. This hypothesis will be tested by assaying separately collected serum samples for HBV markers known to be associated with replication HBsAg and HBV DNA, and a number of recently identified markers which may be directly or inversely associated with replication. These include HB Pre- S1, HB Pre-S2, anti-pol (anti-DNA polymerase), anti-Pre-S1, anti-Pre-S2, HBxAg and anti-HBx. Data collected in Project I including age, sex, clinical, biochemical, and behavioral information will be used as covariates in this project. Factors will be analyzed for their relation to each other, to HBV replication, to chronic liver disease, and their risk of PHC. Univariate and multivariate analyses will be used to identify individual and combination of factors which impact the highest risk. Identification of virus associated risk factors may permit a deeper understanding of the pathogenesis of chronic liver disease and PHC. Identification of individuals at highest risk would identify those persons who would benefit most from therapeutic and preventative intervention strategies. Ideally, knowledge of viral risk factors could lead to the development of methods for preventing serious liver disease from ever occurring.