肝组织HBsAg表达在聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎中的临床意义

发布时间：2018-08-27 09:15

【摘要】：目的:1.探讨IC期肝组织HBV标志物与血清HBV标志物之间的相关性。2.探讨肝组织HBV标志物在预测聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎HBeAg血清学转换中的作用。 方法:回顾性分析2008年1月~2012年1月确诊为IC期的CHB患者，同步收集并分析肝脏组织学及血清学资料， S-P法检测肝细胞中HBsAg、HBcAg表达，采用Spearman等级相关分析探讨肝组织HBsAg、HBcAg表达与血清.HBsAg水平之间的相关性；部分IC期CHB患者给予PEG-IFNα-2a180μg治疗48周，停药后随访24周，，其中发生HBeAg血清学转换的为应答组，未发生HBeAg血清学转换的为无应答组。采用多因素回归法探讨肝组织HBsAg表达对HBeAg血清学转换的预测价值，P0.05表示差异有统计学意义。 结果:1.根据纳入排除标准，共有245例IC期CHB患者纳入本研究。相关性分析提示：肝组织HBsAg表达与血清HBeAg、HBsAg、HBVDNA正相关（r=0.187，P=0.003; r=0.401，P=0.000; r=0.339，P=0.000），而与年龄、ALT、AST、炎症分级及纤维化分期无关；肝组织HBcAg表达与血清HBeAg、HBsAg、HBVDNA正相关（r=0.213，P=0.001； r=0.302，P=0.000；r=0.323，P=0.000），与纤维化分期负相关（r=-0.137，P=0.035），而与年龄、ALT、AST、炎症分级无关。 2.根据纳入与排除标准，本研究共入组患者71例，应答组28例，无应答组43例。48周疗程结束后随访24周，ALT复常率为81.7%（57/71），HBV DNA阴转率为77.5%（55/71），HBeAg血清转换率为39.4%（28/71），HBsAg消失率为7%（5/71），其中有1例（1.4%）实现HBsAg血清学转换。单因素分析结果显示，血清学转换组患者（应答组）肝脏组织HBsAg染色膜表达强度较未转换者（无应答组）低（Z值=-2.0，P=0.045），血清HBsAg定量较无应答组低（3.84±0.95VS4.27±0.61，P=0.029）；应答组与无应答组的性别、年龄、组织炎症及纤维化程度、ALT、HBeAg半定量、HBV DNA、肝内HBsAg、HBcAg水平等指标与HBeAg血清学转换无显著关系。经过二元logistic回归分析结果提示，组织学HBsAg膜表达仍是HBeAg血清学转换的独立预测因素（OR=3.1295%CI=1.062-9.158P=0.039）。 结论:1.IC期CHB患者血清HBsAg浓度可反映肝内HBsAg表达强度；2.肝组织HBsAg膜表达较血清HBsAg更有助于预测PEG-IFNα-2a治疗HBeAg阳性CHB患者的HBeAg血清学应答。
[Abstract]:Purpose 1. To investigate the correlation between HBV markers in liver tissue and serum HBV markers in IC phase. 2. 2. To investigate the role of liver tissue HBV markers in predicting the serological transition of HBeAg positive chronic hepatitis B (HBeAg) with pegylated interferon 伪 -2a (peginterferon 伪 -2a). Methods: the liver histological and serological data were collected and analyzed from January 2008 to January 2012 in CHB patients diagnosed as IC. S-P method was used to detect the expression of HBsAg,HBcAg in hepatocytes. Spearman grade correlation analysis was used to investigate the correlation between the expression of HBsAg,HBcAg in liver tissue and the level of serum. Some CHB patients in IC stage were treated with PEG-IFN 伪 -2a180 渭 g for 48 weeks, followed up for 24 weeks after withdrawal. No HBeAg serological conversion was found in the non-responsive group. Multivariate regression method was used to study the predictive value of HBsAg expression in liver tissue for serological transformation of HBeAg. The result is 1: 1. According to exclusion criteria, a total of 245 patients with IC stage CHB were included in this study. The correlation analysis indicated that the expression of HBsAg in liver tissue was positively correlated with serum HBeAg,HBsAg,HBVDNA (r = 0.187, P ~ (0.003); r = 0.401, P ~ (0.000); ~ (0.339) P ~ (0.000), P ~ (0.000), but not with age, grade of inflammation and stage of fibrosis, the expression of HBcAg in liver tissue was positively correlated with serum HBeAg,HBsAg,HBVDNA (r _ (0.213) P _ (0.001), r ~ (0.302) P ~ + P ~ (0.000), P ~ (0.000), P ~ (0.000), P ~ (0.000). There was a negative correlation with the stage of fibrosis (r = -0.137, P 0.035), but no correlation with the age of ALT and inflammation grade. 2. According to the inclusion and exclusion criteria, there were 71 patients in the study group and 28 patients in the response group. In the non-response group, 43 cases were followed up for 24 weeks after the end of the course of treatment for 24 weeks. The seroconversion rate of HBV DNA was 77.5% (55 / 71). The seroconversion rate of HBeAg was 39.4% (28 / 71), and the disappearance rate of HBeAg was 7% (5 / 71). Among them, 1 case (1.4%) achieved serological conversion of HBsAg. The results of univariate analysis showed that the expression intensity of HBsAg in liver tissue of patients with seroconversion was lower than that of non-responders (Z = -2.0), and the serum HBsAg was lower than that of non-responders (3.84 卤0.95VS4.27 卤0.61), and the sex of responders and non-responders was lower than that of non-responders. Age, tissue inflammation and degree of fibrosis were not significantly correlated with HBeAg serological transformation in patients with ALT HBeAg semi-quantitative HBV-HBV-HBV-HBV-HBeAg intrahepatic HBsAg,HBcAg level. The results of binary logistic regression analysis showed that the expression of histological HBsAg membrane was still an independent predictor of HBeAg serological transformation (OR=3.1295%CI=1.062-9.158P=0.039). Conclusion 1. The concentration of serum HBsAg in CHB patients at IC stage can reflect the expression intensity of HBsAg in liver. The expression of HBsAg in liver tissue was more helpful than serum HBsAg in predicting the HBeAg serological response of HBeAg 伪 -2a patients with HBeAg positive CHB.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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