慢性乙肝患者肝细胞胞浆和胞核的HBcAg表达强度与肝脏炎症纤维化、乙肝病毒复制的关系
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摘要
目的分别评定慢性乙型肝炎(Chronic hepatitis B,CHB)患者肝细胞胞浆和胞核的HBcAg表达强度,分析与临床的关系,研究肝细胞胞浆和胞核内HBcAg的作用。方法对CHB患者肝活检标本317例行免疫组化染色,显示HBc Ag在肝细胞胞浆和胞核的表达强度,同时记录患者的多种临床指标。分别分析肝细胞胞浆和胞核的HBcAg表达强度相互关系以及与各临床指标的关系。结果 HBcAg胞浆和胞核表达强度无相关关系(r=0. 104,P=0. 064)。HBcAg表达胞核阴性组比阳性组呈现年龄更大,ALT、肝组织炎症活动度分级(G)及纤维化分期(S)更高,但血清HBeAg阳性率更低的特点; HBcAg表达胞浆阴性和阳性组两组的上述指标差异均无统计学意义(P>0. 05)。HBcAg胞核和胞浆表达阴性组均比阳性组血清HBVDNA载量更低,差异有统计学意义(P=0. 025,P=0. 00)。结论肝细胞胞核的HBcAg表达强度与肝脏炎症和纤维化联系的紧密性远高于肝细胞胞浆内HBcAg。肝细胞胞核内HBc Ag表达强度可能才是肝脏炎症活跃和纤维化进展的关键,且CHB患者肝细胞胞浆、胞核的HBcAg表达强度均与HBV复制呈正相关。
Objective This paper aims to evaluate the expression level of HBcAg in the cytoplasm and nucleus of the hepatocytes in patients with chronic hepatitis B( CHB),analyze its relationship between with clinical indicators,and study the effects of HBcAg in the cytoplasm and nucleus of the hepatocytes. Methods A total of 317 liver biopsy specimens of patients with CHB were subjected to immunohistochemical staining to expose the expression level of HBcAg in the cytoplasm and nucleus of hepatocytes,and the various clinical indicators of the patients were recorded. The relationship between the expression levels of HBcAg in the cytoplasm and nucleus of hepatocytes and that with the various clinical indicators were analyzed. Results The expression of HBcAg in the cytoplasm and that in the nucleus was not correlated( r = 0. 104,P = 0. 064). Patients with negative HBcAg expression in the nucleus were older than those with positive expression. ALT,inflammation activity grade of liver tissue( G) and fibrosis stage( S) were higher,but the positive rate of serum HBe Ag was lower( P<0. 05). There were no significant differences in the above indexes between the negative HBcAg expression group and the positive HBcAg expression group( P>0. 05). The serum HBV DNA load in the negative HBcAg expression groups in the nucleus and cytoplasm were lower than that in the positive groups( P =0. 025,P = 0. 00). Conclusion The correlation of the HBcAg expression level in the nucleus of hepatocytes with hepatic inflammation and fibrosis is much greater than HBcAg in the hepatic cytoplasm. The expression level of HBcAg in the nucleus of hepatocytes may be key to inflammation and fibrosis progression of the liver. On the other hand,the expression levels of HBcAg in the cytoplasm and nucleus of the hepatocytes of patients with CHB are positively correlated with HBV replication.
Objective This paper aims to evaluate the expression level of HBcAg in the cytoplasm and nucleus of the hepatocytes in patients with chronic hepatitis B( CHB),analyze its relationship between with clinical indicators,and study the effects of HBcAg in the cytoplasm and nucleus of the hepatocytes. Methods A total of 317 liver biopsy specimens of patients with CHB were subjected to immunohistochemical staining to expose the expression level of HBcAg in the cytoplasm and nucleus of hepatocytes,and the various clinical indicators of the patients were recorded. The relationship between the expression levels of HBcAg in the cytoplasm and nucleus of hepatocytes and that with the various clinical indicators were analyzed. Results The expression of HBcAg in the cytoplasm and that in the nucleus was not correlated( r = 0. 104,P = 0. 064). Patients with negative HBcAg expression in the nucleus were older than those with positive expression. ALT,inflammation activity grade of liver tissue( G) and fibrosis stage( S) were higher,but the positive rate of serum HBe Ag was lower( P<0. 05). There were no significant differences in the above indexes between the negative HBcAg expression group and the positive HBcAg expression group( P>0. 05). The serum HBV DNA load in the negative HBcAg expression groups in the nucleus and cytoplasm were lower than that in the positive groups( P =0. 025,P = 0. 00). Conclusion The correlation of the HBcAg expression level in the nucleus of hepatocytes with hepatic inflammation and fibrosis is much greater than HBcAg in the hepatic cytoplasm. The expression level of HBcAg in the nucleus of hepatocytes may be key to inflammation and fibrosis progression of the liver. On the other hand,the expression levels of HBcAg in the cytoplasm and nucleus of the hepatocytes of patients with CHB are positively correlated with HBV replication.
引文
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[15]王功遂,王曼曼,谢秋里,等.HBsAg、HBcAg在慢性乙型肝炎肝细胞内的表达及临床意义[J].中华肝脏病杂志,2004,12(5):287-289.
[16]唐奇远,何清,乐晓华,等.958例慢性乙型肝炎患者肝细胞内HB-c Ag分布规律的研究[J].中西医结合肝病杂志,2010,20(4):204-206.
[17]高敏,卢诚震,王怡,等.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[J].临床肝胆病杂志,2012,28(3):201-204.
[18]盖洪鹏,孙伟翔,袁德胜,等.预存耐药对核普(酸)类似物抗病毒治疗应答和耐药的影响[J].临床肝胆病杂志,2012,28(11):841-844.
[19]He Q,Tang Q,Le X,et al.The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT,HBV DNALevels and HBeAg Status[J].Infection International,2012,1(2):84-90.
[2]Yim HJ,Lok AS.Natural history of chronic hepatitis B virus infection:what we knew in 1981 and what we know in 2005[J].Hepatology(Baltimore,Md.),2006,43(2 Suppl 1):S173-S181.
[3]向光明,钟森,赵川,等.肝细胞癌患者血清乙型肝炎病毒X区及前S/S区基因变异特点[J].中华肝脏病杂志,2007,15(2):146-148.
[4]中华医学会肝病学分会,中华医学会感染病分会.慢性乙型肝炎防治指南2015年更新版[J].临床肝胆病杂志,2015,31(12):1941-1954.
[5]中华医学会传染病与寄生虫病学分会、肝病学分会.病毒性肝炎防治方案[J].中华肝脏病杂志,2000,8(6):324-329.
[6]Scharl A,Vie rbuchen M,Conradt B,et al.Immunohistochemical detection of progeste rone receptor in formalin-fixed and paraffin-embedded breast cancer tissue using a monoc lonal antibody[J].Arch Gynecol Obstet,1990,247(2):63-71.
[7]许良中,杨文涛.免疫组织化学反映结果的判断标准[J].中国癌症杂志,1996,6(4):229-230.
[8]Huang YH,Hung HH,Chan CC,et al.Core antigen expression is associated with hepatic necroinflammation in e antigen-negative chronic hepatitis B patients with low DNA loads[J].Clin Vaccine Immunol,2010,17(6):1048-1053.
[9]Frelin L,Wahlstr m T,Tucker AE,et al.A mechanism to explain the selection of the hepatitis e antigen negative mutant during chronic hepatitis B virus infection[J].J Virol,2009,83(3):1379-1392.
[10]胡滨.不明原因肝病患者隐匿性HBV感染的检测及意义研究.中外医学研究,2014,12(17):68-69.
[11]艾书玲,何清,唐奇远,等.248例慢性乙型肝炎病毒感染者免疫清除期演变规律的研究[J].中国病毒病杂志,2013,3(5):382-386.
[12]Sharma RR,Dhiman RK,Chawla Y,et al.Immunohistochemistry for core andsurface antigens in chronic hepatitis[J].Trop Gastroenterol,2002,23(1):16-19.
[13]刘祖平.慢性乙型肝炎肝细胞HBsAg,HBcAg表达与肝组织病理学分析[J].中国卫生检验杂志,2015,25(10):1591-1593.
[14]张香梅,乐晓华,王敏,等.乙型肝炎肝细胞内HBcAg表达模式与肝组织炎症及血清学指标的关系[J].临床与实验病理学杂志,2014,30(6):686-688.
[15]王功遂,王曼曼,谢秋里,等.HBsAg、HBcAg在慢性乙型肝炎肝细胞内的表达及临床意义[J].中华肝脏病杂志,2004,12(5):287-289.
[16]唐奇远,何清,乐晓华,等.958例慢性乙型肝炎患者肝细胞内HB-c Ag分布规律的研究[J].中西医结合肝病杂志,2010,20(4):204-206.
[17]高敏,卢诚震,王怡,等.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[J].临床肝胆病杂志,2012,28(3):201-204.
[18]盖洪鹏,孙伟翔,袁德胜,等.预存耐药对核普(酸)类似物抗病毒治疗应答和耐药的影响[J].临床肝胆病杂志,2012,28(11):841-844.
[19]He Q,Tang Q,Le X,et al.The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT,HBV DNALevels and HBeAg Status[J].Infection International,2012,1(2):84-90.