原发性肝癌是一种常见的恶性肿瘤，HBV是其发生发展最重要的因素之一。中国是全世界HBsAg阳性率最高的国家。另一方面，由饮食和生活习惯改变导致的肥胖及代谢综合征趋于流行，脂肪肝发生率不断攀升，慢性HBV感染合并脂肪肝患者也越来越多。脂肪肝与HBV感染对病毒应答及疾病进展（尤其是肝癌发生）的交互作用是当前肝病研究的热点。因此，本项目基于多中心优势互补的社区和治疗慢性HBV感染者前瞻性的大样本人群研究结果，探讨脂肪肝与HBV病毒应答及肝癌发生的关联。并建立脂肪肝通过抑制HBV复制进而影响肝癌发生的中介效应模型。进一步建立乙肝感染合并高脂饮食的小鼠模型，从宿主、病毒两方面，探讨肝脏脂肪化是否是通过调节免疫应答影响HBV复制进而影响肝癌发生的潜在机制。研究结果对于完善HBV致癌机制的认知和慢乙肝合并脂肪肝的病人的临床管理有重大的理论和实际指导意义。

Hepatocellular carcinoma is one of the most popular cancers, chronic HBV infection is the most important risk factor. China has the greatest number of HBsAg-positive people worldwide. With the growing prevalence of obesity and metabolic syndrome (MS) caused by dominance of over-rich diet and sedentary life style, the incidence rate of hepatic steatosis disease keeps on increasing, many patients suffer from both HBV infection and steatosis. The impact and interaction of HBV and steatosis in virus response and development of CHB are of great concern, especially in HCC occur. Therefore, we used two complementary prospective cohort studies (from community- and hospital-based population) to explore whether steatosis influence HBV replication and HCC development. Then a mediation analysis was established to evaluate whether steatosis influence HCC occur through inhibiting HBV replication. In consideration of host and virus, we established a mouse model of hepatitis B infection with high fat-diet to investigate whether steatosis inhibiting virus replication through regulating immune response then playing a role in HCC onset. The results are of great theoretical and practical significance for improving the understanding of the carcinogenic mechanism of HBV and clinical management of patients with chronic hepatitis B complicated with fatty liver.