HBV慢性感染者前C/BCP区变异特点及与疾病发展关系分析

Relationship analysis of PreC/BCP mutation characteristicsand disease development in chronic HBV infected patients

目的:探讨慢性HBV感染者前C/BCP区突变与血清HBeAg、HBs Ag、DNA、甲胎蛋白(AFP)及肝硬度值(LSM)的关系及对疾病进展的预测性。方法:收集101例未经抗病毒治疗的慢性HBV感染者和47例乙型肝炎肝硬化(LC)患者清晨空腹血清。以免疫化学发光法检测血清HBeAg、HBs Ag、AFP含量,采用磁珠法检测HBV-DNA,应用半巢式聚合酶链反应检测前C/BCP区基因突变,采用无创实时检测设备检测LSM。结果:101例慢性HBV感染者中,HBeAg阴性组的前C、BCP、前C+BCP区的变异率显著高于HBeAg阳性组(P<0.01)。而LC组总变异率显著高于慢性HBV感染者HBeAg阴性组和HBeAg阳性组(P<0.01)。148例HBV感染者中前C区、BCP区和前C+BCP变异株共87例,野生株61例,变异型组与野生型组比较,HBeAg含量减少(P<0.05),HBs Ag含量增加(P<0.01),AFP水平和LSM值增高(P<0.05),DNA水平无统计学意义(P>0.05)。结论:HBeAg阴性的慢性HBV感染患者中前C/BCP区变异率较高,变异可能导致更易发展为肝硬化,病情加重。监测HBeAg阴转的慢性HBV感染患者的DNA、HBs Ag、AFP、LSM指标,对了解病情及体内病毒是否确实已被免疫清除有参考价值。

Objective： To investigate relationshipsamong Pre C/BCP mutation and serum HBeAg,HBs Ag,DNA,AFP levels and liver stiffness measurement（ LSM） in patients with chronic HBV infections,and to analyze their predictionsin disease progression.Methods： The subjects were 101 patients with chronic HBV infections and 47 patients with hepatitis B liver cirrhosis. They were all not given the antiviral treatment,and the early morning fasting blood serum specimens were collected. The serum levels of HBeAg,HBs Ag and AFP were detected by chemiluminescent immunoassay,the HBV-DNA was detected by magnetic beads assay,and the Pre C/BCP gene mutations were detected by semi-nested polymerase chain reaction. LSM was measured by noninvasive real-time detection equipment. Results： In the 101 cases with chronic HBV infections,the mutation rate of the Pre C,BCP and Pre C＋BCP in the HBeAg negative group was significantly higher than that in the HBeAg positive group（ P〈0.01）. The total muation rate in the LC group was significantly higher than that in HBeAg negative group and HBeAg negative group of thechronic HBV infection patients（ P〈0.01）. Among the148 cases,there were 87 cases with the Pre C,BCP and Pre C＋BCP variants and 61 cases with the wild strains. Compared with the mutant group,the HBeAg content decreased（ P〈0.05）,the HBs Ag increased（ P〈0.01）,and the AFP level and LSM values increased（ P〈0.05）; however,there was no significant difference in the DNA level. Conclusions： In the chronic HBV infection patients with negative HBeAg,the mutation rate in the Pre C/BCP region is higher,and the mutations can prone to lead to cirrhosis and exacerbations. Therefore,it should monitor the indicators like DNA,HBs Ag,AFP,and LSM of them,which is valuable for understanding the disease and whether the virus in the body has indeed been immunosuppressed.