HCV感染后病毒和宿主因素致肝硬化及肝癌前瞻性队列研究

Hepatitis C infection is a very important risk factor that leads to cirrhosis and liver cancer. Occult onset of hepatitis C infection in some patients develop into cirrhosis leading to liver cancer, of which there are a few with rapid disease progression. Some patients can spontaneously clear HCV virus; some patients although infected with HCV, the liver shows no obvious pathological damage, and the prognosis is good . The study of the natural history of patients with hepatitis c with different outcomes is the lack of data, especially research data from Chinese database. Field epidemiological investigation was carried out for a cohort of 6987 people from Jilin Province who shared syringes and found that hepatitis C infection rate was as high as 40.7% ,of which 763 people were treated with interferon α-2b and ribavirin antiviral. An observation of host factors like the IL-28B, IP-10, CD24 gene polymorphism, interleukin-33 level, and NK cell activity and others; viral factors such as viral load and genotype, and environmental factors on disease progression and response to treatment were assessed. Now after 4 years of follow-up of the infected group, our intention is to continue to follow-up based on impact factors, changes in condition of variable mechanism and efficacy evaluation, in order to understand the natural evolution of HCV infection in China and to propose a new strategy of China's hepatitis C diagnosis and treatment follow-up.

丙肝感染是导致肝硬化、肝癌非常重要的危险因素。丙型肝炎起病隐匿，感染后有些病人发展成肝硬化肝癌，这其中又有少数进展迅速；部分病人能够自发清除HCV病毒；有些病人虽感染了HCV，但肝脏没有明显的病理损害，预后良好。有关丙肝病人不同结局的自然史的研究缺乏数据，特别是中国的研究数据。本研究前期已对吉林省6987名共用注射器的人群进行了现场流行病学调查，发现该人群中丙型肝炎感染率高达40.7%，对其中763人进行干扰素α-2b联合利巴韦林的抗病毒治疗。并且观察了IL-28B，IP-10，CD24的基因多态性，白细胞介素33水平，和NK细胞活性等宿主因素，病毒载量和基因型等病毒因素，和其他人口，环境因素对疾病进展，治疗应答的影响。现已对这群感染者随访了4年。拟在此基础上对其进行继续随访，以了解我国人群HCV感染的自然演变规律，影响因素，病情变化变机制和疗效评价，提出我国的丙肝诊断治疗随访的新策略。

丙肝感染是导致肝硬化、肝癌非常重要的危险因素，有关丙肝病人不同结局的自然史的研究缺乏数据。本研究前期已对吉林省6987名共用注射器的人群进行了现场流行病学调查，现已对这群感染者随访了8年，以了解我国人群HCV感染的自然演变规律，影响因素，病情变化变机制和疗效评价，提出我国的丙肝诊断治疗随访的新策略。我们选择了HCV感染比较集中吉林省扶余县为调查点，研究HCV感染者肝硬化和肝癌发展的速度和发生率；观测HCV感染者终末期肝脏疾病发生率和死亡率，分析病毒、环境、特别是宿主因素对HCV病毒自然清除的影响；病毒宿主因素对肝脏纤维化，肝硬化和肝癌进展的影响；寻找影响疾病进展的预测因子；研究HCV感染导致的肝硬化患者血清中M2BP蛋白的浓度变化，及分析了其预测肝硬化的能力。研究发现公用注射器注射安纳咖是该地HCV流行的重要因素；IFNL4 ss154949590 TT/TT基因型利于HCV的自发清除，也有利于1b型感染患者的治疗应答。对于1b型高病毒载量的慢丙肝患者，应该进行基因分型；CD24基因表达水平及P170 位点单核苷酸多态性均与丙型肝炎自发清除相关，提示可能是丙肝自然转归的预测因子之一；在HCV 1b型感染者中，COMT rs4818 GG基因型比CC/GC基因型获得更高的治疗结束时病毒学应答率（ETVR）和持续病毒学应答率（SVR）；CYP2R1基因rs10741657位点AA基因型有利于丙肝患者获得快速病毒学应答和完全早期病毒学应答；GC基因编码维生素D结合蛋白基因，该基因上的rs222020 位点的TC基因型有利于丙肝患者获得较高水平的病毒学应答率。随着肝纤维化分期的升高，CHC患者血清M2BPGi水平逐渐升高。