近年来，全基因组关联研究（GWAS）发现了多个慢性HBV感染及肝癌相关的易感区域/位点，但这些易感位点在人群肝硬化及肝癌风险预测中的转化应用价值尚未明确。传统的风险预测模型仅考虑HBV相关危险因素，并没有纳入遗传易感位点及环境暴露因素（如黄曲霉毒素）这类已知的与肝硬化及肝癌发生发展密切相关的危险因素。因此，本项目拟在课题组自2009年起建立的社区慢性HBV感染者前瞻性队列的基础上，开展一项设计全面的肝硬化及肝癌危险因素及风险预测模型研究，综合病毒、遗传、环境及端粒长度多方面因素评价和预测江苏人群肝硬化/肝癌的发病风险。本课题拟首先通过队列的前瞻性随访（可达3万人年）分析影响肝硬化/肝癌发生发展的危险因素，再将遗传标志物和传统危险因素相结合建立肝硬化/肝癌风险预测模型，最后评估风险预测模型的价值。本研究成果有望用于人群肝硬化/肝癌风险预测和高危人群筛查，为实施个体化的预防和早诊早治提供新工具

Currently, several genome-wide association studies (GWAS) have identified novel susceptibility loci on chronic hepatitis B virus (HBV) infection and related hepatocellular carcinoma (HCC). However, it is still unknown regarding clinical utility of these loci in the HCC risk prediction in Chinese population. Several HCC risk prediction models have been published; however, most are limited by HBV characteristics. Other important risk factors for HCC, such as host genetic background and aflatoxin exposure, have not been considered. On the basis of the community-based prospective cohort in chronic HBV infection we conducted in 2009, this project is proposed to integrate HBV characteristics, genetic markers and environmental factors to develop models for predicting HCC risk in chronic HBV patients. Newly developed HCC cases were ascertained through regular follow-up with an estimated 30,000 person-years to identify HCC related risk factors. In combination of genetic markers and traditional HCC related risk factors, we further plan to develop risk model for HCC risk prediction in Chinese population and evaluate the predictive accuracy of the risk prediction models. The study results in this project will be used to predict HCC risk in chronic hepatitis B patients, screen high-risk populations, and provide a new tool for early prevention, diagnosis and treatment for HCC.