目的调查HBV感染不同转归人群外周血程序性死亡受体-1(PD-1)基因拷贝数(CN)分布频率的差异。方法在300例HBV感染恢复者、437例慢性乙型肝炎(CHB)、249例肝硬化(LC)和123例肝细胞癌(HCC)患者,采用AccuCopy法检测外周血PD-1基因拷贝数。选择5个可能影响慢性HBV感染结局的指标,即HBeAg滴度、年龄、性别、HBV DNA和PD-1拷贝数,行Logistic回归分析,以发现影响感染结局的指标。结果HBV感染恢复者、CHB、LC和HCC组外周血PD-1单倍体检出率分别为11.7%、9.6%、6.0%和10.6%,多倍体检出率分别为89.3%、90.4%,94%和89.4%,显示LC组多倍体检出率显著高于HBV感染恢复组或HCC组(P<0.05);以CHB组作为估计参数,经Logistic回归分析发现年龄和血清HBV DNA载量为影响疾病转归的独立危险因素。结论本研究结果提示影响HBV感染转归的因素还是病毒本身和患者年龄,而外周血PD-1基因拷贝数变异检测的意义还有待于进一步研究。
Objective To explore whether copy number variations(CNVs) of blood programmed cell deathl(PD-1) are associated with outcomes of hepatitis B virus(HBV) infection. Methods 300 convalescent individuals from HBV infection,437 patients with chronic hepatitis B(CHB),249 patients with liver cirrhosis(LC)and 123 patients with hepatocellular carcinoma(HCC) were recruited in this study,and peripheral blood copy numbers of PD-1 gene were measured by using AccuCopy method. x~2 tests were used to evaluate the distribution differences of copy number variations(CNVs) of PD-1 in different clinical types of HBV infections. The Logistic regression analysis was used to analyze the independent risk factors for severe outcome of the disease. Results In 1109 samples,the variation range of PD-1 gene copy number was 1 to 3 copies. The haploid rates in convalescent individuals,patients with CHB,with LC and with HCC were 11.7%,9.6%,6.0% and 10.6%,respectively,and the polyploid rates in these four groups were 89.3%,90.4%,94% and 89.4%,demonstrating that there were significant differences between convalescent individuals and patient with LC,or between patient with HCC and with LC(P <0.05);The Logistic analysis showed that the age and serum HBV DNA loads were the independent risk factors affecting the prognosis of the disease. Conclusions Our results indicate that the patient’s age and serum HBV DNA levels are the risk factors which might determine the prognosis of patients with HBV infection,while what roles the CNVs of PD-1 play in the pathogenesis of hepatitis B viral infection needs further observation.
Journal of Practical Hepatology