慢性乙型肝炎病毒感染者肝组织HBcAg表达与临床及病理特征的关系

目的探讨慢性HBV感染者肝组织HBcAg表达及其在亚细胞结构的分布与血清HBeAg表达、HBV DNA水平及肝组织病理学损害的关系。方法对371例慢性HBV感染者进行肝穿刺活检,检测肝组织HBcAg、血清HBV标志物、血清ALT及血清中的HBV DNA水平。比较HBcAg阴性与HBcAg表达为核型、浆型、浆核型的病例血清HBeAg阳性率、HBV DNA水平与肝组织病理学损害的关系。同时观察血清HBeAg阳性组及阴性组,肝细胞HBcAg不同表达形式在不同年龄阶段的分布特点。结果肝组织HBcAg阴性组血清HBeAg阳性率为33.1%,比HBcAg阳性各组均低(核型组68.7%;浆型组62.3%;浆核型组84.5%),炎症分级G≥2的患者比例为21.5%,低于HBcAg阳性各组(核型34.3%;浆型67.7%;浆核型69.1%),P<0.01,差异有统计学意义。其中浆型组及浆核型组G≥2的患者比例高于核型组,P<0.01,差异有统计学意义。血清HBV DNA水平在核型组高于其他各组,P<0.05,差异有统计学意义。血清HBeAg阳性组中,年龄≤20岁的HBcAg肝细胞表达为核型的比例为61.5%,高于年龄为20～39岁的11.5%及年龄≥40岁的12.3%,随年龄增加浆型及浆核型表达的比例增加,在三组分别为23.1%/7.7%、26.4%/30.8%、28.4%/45.4%,差异有统计学意义(χ2=53.74,P<0.01)。血清HBeAg阴性组中,肝组织HBcAg阴性的在各年龄组均占大部分(68.1%、61.5%、40.4%)。随年龄增加浆型及浆核型表达的比例增加,在三组分别为4.6%/4.6%、19.3%/7.7%、26.9%/20.4%,差异无统计学意义(χ2=8.94,P>0.05)。结论慢性乙型肝炎患者肝组织HBcAg表达与血清HBeAg表达有关。浆型及浆核型HBcAg表达常伴随明显的肝组织炎症。HBcAg表达形式在不同年龄阶段具有不同特点,与其所处自然史阶段有关。

Relationship between expression of HBcAg in liver tissue and characteristics of the hepatic pathological features in patients with chronic hepatitis B virus infection

Objective To explore the relationship between expression of HBcAg in liver tissue,subcellular localization of HBcAg and serum HBeAg expression,and level of HBV replication and histologic activity.Methods We enrolled 371 patients with chronic hepatitis B virus infection who underwent liver biopsy at Tianjin Infectious disease Specialty Hospital between 2008-2010.The levels of alanine aminotransferase and HBV DNA level were simultaneously measured.The positive rate of serum HBeAg,the level of HBV DNA.histologic activity in the patients with negative expression of HBcAg and nHBcAg,cHBcAg,n-cHBcAg expression were compared.At the same time,delect the difference of the expression of HBcAg at different age-stage in HBeAg-positive patients and HBeAg-negative was observed.Results The seropositive rate of HBeAg was 33.1% in patients with negative expression of HBcAg,68.7% in those with nHBcAg,62.3% in those with cHBcAg,and 84.5% in those with n-cHBcAg(P<0.01).The percentage of patients with G≥2 was lower(21.5% vs.34.3%、67.7%、69.1%,P<0.01) for the negative expression of HBcAg(cHBcAg) than for the nHBcAg 、cHBcAg、 c-nHBcAg expression.Among them,the percentage of patients with G≥2 for the cHBcAg and c-nHBcAg expression is higher than the nHBcAg expression(P<0.01).The serum HBV DNA level was higher in nHBcAg among the groups.Among the serum HBeAg positive group,the expression rate of nHBcAg in≤20 age stage,20-39 age stage and ≥40 age stage was 61.5%,11.5% and 12.3% respectively.The age-dependent increase of cHBcAg、c-nHBcAg expression rate was observed(23.1%/7.7%;26.4%/30.8%;28.4%/45.4%),there was a statistical significance in the difference(χ2=53.74,P<0.01).Among the cases in serum HBeAg negative group,the negative rate for HBcAg in≤20 age stage,20-39 age stage and ≥40 age stage was 68.1%,61.5% and 40.4% respectively.The age-dependent increase of cHBcAg、 c-nHBcAg expression rate was observed.(4.6%/4.6%;19.3%/7.7%;26.9%/20.4%),but there was no significant difference(χ2=8.94,P>0.05).Conclusion The expression of HBcAg for the patients with chronic hepatitis B virus infection was related to the serum HBeAg expression.The histologic grade of hepatitis were significantly correlated with the subcellular localization of intrahepatic HBcAg.There were different characteristic for the expression of HBcAg in the different age stage,perhaps due to the different natural history stage.