慢性乙型肝炎病毒感染者994例肝组织HBsAg和HBcAg表达强度的临床意义

Expression intensity and clinical significance of intrahepatic hepatitis B surface antigen and hepatitis B core antigen in 994 patients with chronic hepatitis B virus infection

目的 分析慢性乙型肝炎病毒（HBV）感染者肝组织HBsAg和HBcAg的表达强度及临床意义.方法 收集994例接受肝脏穿刺活检术及组织病理学检查的慢性HBV感染者的临床资料,根据乙型肝炎e抗原（HBeAg）及HBV DNA水平分为HBeAg（＋）/HBV DNA（＋）组、HBeAg（-）/HBV DNA（＋）组及HBeAg（-）/HBV DNA（-）组;根据肝组织HBsAg和HBcAg免疫组织化学染色分为阳性组和阴性组;根据丙氨酸转氨酶（A LT）的水平分为＜2×正常值上限（ULN）组、2-＜5×ULN组及≥5×ULN组.研究肝组织炎症活动度（A）、纤维化分期（F）及肝组织HBsAg和HBcAg的表达强度,分析其与临床特征的相关性.Logistic回归分析影响肝组织HBsAg和HBcAg表达强度的相关因素.结果 994例慢性HBV感染者中,肝组织HBsAg染色阳性941例（94.67％）,肝组织HBcAg染色阳性553例（55.63％）;≥A2者403例（40.85％）,≥F2者371例（36.09％）.HBeAg（-）/HBV DNA（＋）组的A和F最严重,其次为HBeAg（-）/HBV DNA（-）组,HBeAg（＋）/HBVDNA（＋）组最低;虽然三组间肝组织HBsAg染色强度的总体差异有统计学意义（Х^2=6.299,r=-0.760,P＜0.05）,但两两比较差异均无统计学意义;三组间肝组织HBcAg染色强度的总体差异有统计学意义（Х^2=282.995,r=-0.645,P＜0.01）,以HBeAg（＋）/HBV DNA（＋）组最高、HBeAg（-）/HBV DNA（-）组最低.肝组织HBsAg染色阳性组HBeAg阳性的构成及HBV DNA平均水平均高于阴性组,年龄低于阴性组;肝组织HBcAg染色阳性组HBeAg阳性的构成、ALT、天门冬氨酸转氨酶（AST）、血小板（PLT）及HBV DNA平均水平均高于阴性组,年龄及FIB-4低于阴性组;影响肝组织HBsAg染色的因素为HBV DNA水平;影响肝组织HBcAg染色的因素为HBeAg阳性及HBV DNA水平.肝组织HBsAg不同染色强度间A和F的总体差异均无统计学意义（Х^2=1.943和2.630,P值均＞0.05）;肝组织HBcAg不同染色强度间A的总体差异无统计学意义,而F的总体差异有统计学意义（Х^2=12.352,P＜0.01）,以阴性组的F最严重.ALT不同水平组肝组织HBsA染色强度的差异无统计学意义;肝组织HBcAg染色强度的差异有统计学意义（Х^2=16.349,P＜0.01）,ALT＜2×ULN组均低于其他组.结论 慢性HBV感染者中绝大数肝组织HBsAg染色阳性,超过半数肝组织HBcAg染色阳性;肝组织HBsAg的表达强度与A和F无相关性,与HBV DNA水平正相关;肝组织HBcAg的表达强度与A无相关性,与F负相关,与HBeAg阳性、HBV DNA及ALT水平正相关.

Objective To investigate the intensity of HBsAg and HBcAg expression in liver tissue of patients with chronic hepatitis B virus （HBV） infection and its clinical significance.Methods A total of 994 HBV infected patients underwent liver biopsy and histopathological examination.The expression of HBsAg and HBcAg in liver tissue was detected by histoimmunochemistry.Patients were divided into HBeAg （＋）/HBVDNA（＋）, HBeAg（-）/HBV DNA（＋） and HBeAg（-）/HBV DNA（-） groups according to HBeAg and HBV DNA levels;patients were divided into 〈2 × normal （ULN） group, 2-〈5 × ULN groupand ≥5 × ULN group according to the alanine aminotransferase （ALT） levels.The histologic activity （A）, fibrosis （F）, the expression of HBsAg and HBcAg in liver tissue and their correlations with clinical features were analyzed.Logistic regression analysis was used to study the factors affecting the expression of HBsAg and HBcAg in liver tissue.Results Among 994 HBV infected patients, 941 cases （94.67%） were intrahepatic HBsAg positive and 553 cases （55.63%） were intrahepatic HBcAg positive;403 cases （40.85%） were ≥A2 in histologic activity and 371 cases （36.09%） were ≥F2 in fibrosis.The degree of A and F was the highest in HBeAg （-） / HBV DNA （＋） group, followed by HBeAg （-） / HBV DNA （-） group, and was the lowest in HBeAg （＋） / HBV DNA （＋） group.The intensity of intrahepatic HBsAg expression was significantly different among three groups （Х^2 =6.299, r =-0.760, P 〈 0.05）, however, the difference was not showed in pairwise comparisons.The difference of intrahepatic HBcAg intensity among three groups was statistically significant （Х^2 =282.995, r =-0.645, P 〈 0.01）, the intensity was the highest in HBeAg （＋） / HBV DNA （＋） group and the lowest in HBeAg （-） / HBV DNA （-） group.The constituent ratio of HBeAg positive and HBV DNA level were higher and the average age was lower in intrahepatic HBsAg positive group than those in HBsAg negative group.The constituent ratio of positive HBeAg, the levels of ALT, AST, PLT and HBV DNA were higher and the average age, the average FIB-4 level were lower in intrahepatic HBcAg positive group than those in HBcAg negative group.The HBV DNA level was an independent risk factor for intrahepatic HBsAg intensity, and the HBeAg positive and HBV DNA level were independent risk factors for intrahepatic HBcAg intensity.There were no significant differences in A and F among different groups of intrahepatic HBsAg intensity （Х^2 =1.943 and 2.630, both P 〉 0.05）.There was significant difference in F among different groups of intrahepatic HBcAg intensity （Х^2 =12.352, P 〈 0.01）, but not in A.The degree of F was the highest in intrahepatic HBcAg negative group.There was significant difference in intrahepatic HBcAg intensity among different groups of ALT level （Х^2 =16.349, P 〈 0.01）, but not in intrahepatic HBsAg intensity.The intrahepatic HBcAg intensity in ALT 〈 2 × ULN group was lower than that in other two groups.Conclusions Most of patients with chronic HBV infection are intrahepatic HBsAg positive and more than half of them are intrahepatic HBcAg positive.The intrahepatic HBsAg intensity is not associated with A and F, but correlates with HBV DNA level.The intrahepatic HBcAg intensity is not associated with A, but it is negatively correlated with F and positively correlated with positive HBeAg expression, HBV DNA level and ALT level.