慢性乙型肝炎患者免疫耐受和活动状态肝组织内HBsAg和HBcAg表达差异

Differences in HBsAg and HBcAg expression in liver tissues between chronic hepatitis B patients with immunologic tolerance vs immune activity

目的分析慢性乙型肝炎(chronic hepatitis B,CHB)患者在乙型肝炎病毒(hepatitis B virus,HBV)感染免疫耐受和活动状态的临床和病理学差别.方法选择102例CHB免疫耐受期患者组成免疫耐受组,215例CHB免疫清除期或再活动期患者组成免疫活动组,分析两组间肝组织内乙型肝炎病毒表面抗原(hepatitis B surface antigen,HBsA g)和乙型肝炎核心抗原(hepatitis B core antigen,HBc Ag)的表达、性别、谷丙转氨酶、血清HBV DNA载量、肝脏炎症活动度分级(G)和纤维化分期(S)的差异.结果免疫耐受组的HBs Ag胞膜表达强度低于免疫活动组(P=0.037),而肝组织内HBc Ag表达强度、HBc Ag胞核表达强度显著高于免疫活动组(P=0.00).仅在免疫活动组,肝组织内HBs Ag表达强度与HBV DNA存在正相关性(P=0.019),肝组织内HBc Ag表达强度、HBc Ag胞浆和胞核表达强度与HBV DNA均存在正相关性(均P<0.05);肝组织内的HBc Ag表达强度和HBc Ag胞核表达强度与G、S存在负相关性(均P<0.05).仅在免疫耐受组,肝组织内的HBsAg胞浆表达强度与G、S存在正相关性(P=0.016和P=0.003).结论肝组织内的HBs Ag胞膜表达强度与CHB免疫活动程度呈正相关.肝细胞胞浆内表达的HBsAg有可能系免疫耐受状态机体攻击的靶抗原.肝细胞核内表达的HBc Ag即是CHB病毒复制,又是免疫耐受状态的打破进展至免疫活动状态的关键,也是肝组织炎症活跃和纤维化进展的关键.

AIM To address the clinical and pathological differences between chronic hepatitis B（CHB）patients with immune tolerance vs immune activity for hepatitis B virus（HBV）.METHODS One hundred and two patients in CHB immune tolerance phase were assigned to the immune tolerance group,and 215 patients in CHB immune clearance or reactivation phase were assigned to the immune activity group.The two groups were compared for differences in hepatitis B surface antigen（HBsAg） and hepatitis B core antigen（HBcAg） expression in liver tissues,gender,alanine transaminase,serum HBV DNA load,liver inflammatory activity grade,and fibrosis stage.RESULTS Membrane HBsAg expression intensity in liver tissues was lower in the immune tolerance group than in the immune activity group（P= 0.037）.HBcAg expression intensity in liver tissues and nuclear HBcAg expression intensity were significantly higher in the immune tolerance group than in the immune activity group（P = 0.00）.In the immune activity group,HBsAg expression intensity in liver tissues was positively correlated with HBV DNA load（P = 0.019）,and HBcAg expression intensity in liver tissues,plasma HBcAg expression intensity and nuclear HBcAg expression intensity were all positively correlated with HBV DNA load（P〈0.05 for all）,while HBcAg expression intensity in liver tissues and nuclear HBcAg expression intensity were negatively correlated with liver inflammatory activity grade and fibrosis stage（P〈0.05 for both）.In the immune tolerance group,cytoplasmic HBsAg expression intensity in liver tissues was positively correlated with liver inflammatory activity grade and fibrosis stage（P = 0.016 and P = 0.003,respectively）.CONCLUSION Membrane HBsAg expression intensity in liver tissues is positively correlated with the CHB activity;cytoplasmic HBsAg expression in liver cells might provide the target antigen in the immune tolerance phase.HBcAg expression in liver cell nucleus is not only key to both CHB replication,the breaking of immune tolerance and its progression into immune activity,but also essential for inflammatory activity and fibrosis progression in liver tissues.