CAJ | 학술논문

目的探讨乙型肝炎病毒X蛋白(HBxAg)在HBV感染相关性肝病患者病情进展和癌变过程中的作用. 方法用免疫组织化学方法检测38例HBV慢性感染者(HBV携带者14例及慢性乙型肝炎患者24例)、20例乙型肝炎肝硬化(LC)和20例HBV相关性肝细胞癌(HCC)患者肝组织中HBxAg、Fas及其配体(FasL)的表达,分析HBxAg与Fas、FasL表达的相关性及其与患者病毒学指标和肝脏病理学改变的关系.肝脏炎症分级及纤维化分期按照Knodell标准.计数资料用x2检验及Fisher精确概率法,多个样本间的两两比较用x2分割法,等级资料用秩和检验,相关性分析采用Spearman等级相关分析. 结果 HBV慢性感染者、LC及HCC患者肝组织中HBxAg阳性率分别为71.1％、60.0％、65.0％,差异无统计学意义(x2=0.754,P＞0.05).肝细胞中Fas和FasL阳性率分别为28.9％、20.0％、5.0％和36.8％、50.0％、60.0％,各组间差异均无统计学意义(x2值分别为4.667和2.988,P值均＞0.05).三组患者肝组织淋巴细胞Fas表达的阳性率分别为68.4％、60.0％和90.0％,其中,肝癌患者的表达强度显著高于HBV慢性感染者(Z=-4.360,P＜0.01).在LC重症炎症区域及部分HCC患者中可见HBxAg与FasL在同一区域表达.相关性分析显示,HBV慢性感染和LC患者中,HBxAg与Fas、FasL表达强度均具有相关性(r值分别为0.304和0.368,P值均＜0.05),Fas与FasL的表达也存在相关性(r=0.448,P＜0.01).HBxAg阳性率在高、中病毒载量组(分别为88.9％和69.2％)均明显高于低病毒载量组(为26.7％,P＜0.05). 结论 HBxAg在HBV感染各期均起重要作用,早期主要上调肝细胞Fas表达并诱导肝细胞凋亡,使肝脏炎症坏死加重；后期主要上调肝细胞FasL表达并诱导免疫逃避.HBxAg和高病毒载量在HBV慢性感染者病情发展和癌变中起重要作用.
목적 탐토을형간염병독X단백(HBxAg)재HBV감염상관성간병환자병정진전화암변과정중적작용. 방법 용면역조직화학방법검측38례HBV만성감염자(HBV휴대자14례급만성을형간염환자24례)、20례을형간염간경화(LC)화20례HBV상관성간세포암(HCC)환자간조직중HBxAg、Fas급기배체(FasL)적표체,분석HBxAg여Fas、FasL표체적상관성급기여환자병독학지표화간장병이학개변적관계.간장염증분급급섬유화분기안조Knodell표준.계수자료용x2검험급Fisher정학개솔법,다개양본간적량량비교용x2분할법,등급자료용질화검험,상관성분석채용Spearman등급상관분석. 결과 HBV만성감염자、LC급HCC환자간조직중HBxAg양성솔분별위71.1％、60.0％、65.0％,차이무통계학의의(x2=0.754,P＞0.05).간세포중Fas화FasL양성솔분별위28.9％、20.0％、5.0％화36.8％、50.0％、60.0％,각조간차이균무통계학의의(x2치분별위4.667화2.988,P치균＞0.05).삼조환자간조직림파세포Fas표체적양성솔분별위68.4％、60.0％화90.0％,기중,간암환자적표체강도현저고우HBV만성감염자(Z=-4.360,P＜0.01).재LC중증염증구역급부분HCC환자중가견HBxAg여FasL재동일구역표체.상관성분석현시,HBV만성감염화LC환자중,HBxAg여Fas、FasL표체강도균구유상관성(r치분별위0.304화0.368,P치균＜0.05),Fas여FasL적표체야존재상관성(r=0.448,P＜0.01).HBxAg양성솔재고、중병독재량조(분별위88.9％화69.2％)균명현고우저병독재량조(위26.7％,P＜0.05). 결론 HBxAg재HBV감염각기균기중요작용,조기주요상조간세포Fas표체병유도간세포조망,사간장염증배사가중；후기주요상조간세포FasL표체병유도면역도피.HBxAg화고병독재량재HBV만성감염자병정발전화암변중기중요작용.
Objective To study the roles of hepatitis B virus (HBV) X antigen (HBxAg) in development of HBV-related liver diseases and carcinogenesis.Methods Liver tissues were collected from patients with HBV infection (HBV carriers,n =14; chronic hepatitis B (CHB),n =24),HBV-related liver cirrhosis (LC,n =20),or hepatocellular carcinoma (HCC,n =20).Immunohistochemistry was used to detect the expression of HBxAg and the host apoptosis-related genes Fas and Fas ligand (Fas-L).The correlations of HBxAg with HBV DNA level in serum,inflammation grade,and fibrosis stage were statistically analyzed.Liver inflammation grade and fibrosis stage were in accordance with Knodell standard.x2 test and Fisher's exact test were adopted in count data,x2 split method was adopted in pariwise comparisons between multiple samples,Rank-sum test was adopted in ranked data,Spearman rank correlation analysis was adopted in correlation analysis.Results The rates of HBxAg-positivity were similar between the patients with HBV infection (71.1％),LC (60.0％),and HCC (65.0％) (x2 =0.754,P =0.686).The rates of Fas-and Fas-L-positivity in liver cells were also similar between the three groups (Fas:28.9％ vs.20.0％ vs.5.0％,x2 =4.667,P =0.101; Fas-L:36.8％ vs.50.0％ vs.60.0％,22 =2.988,P =0.225).However,the positive rate of Fas in lymphocytes of liver tissue was significantly higher in the HCC patients than in the HBV-infected patients (90.0％ vs.68.4％,Z =-4.360,P =0.00001).The expressions of HBxAg and Fas-L corresponded to regions of severe inflammation in tissues from LC patients and some HCC patients.Furthermore,the expression of HBxAg was positively correlated with Fas (r =0.304,P =0.02) and Fas-L (r =0.368,P =0.004) in the HBV-infected patients and LC patients,and the expression of Fas was positively correlated with that of Fas-L (r =0.448,P =0.0004).Patients with high and medium loads of HBV DNA showed significantly higher rates of HBxAg-positivity than those with low loads (88.9％ and 69.2％ vs.26.7％,P ＜ 0.05).Conclusion In the early stage of chronic HBV infection,HBxAg may induce liver cell apoptosis by up-regulating Fas expression,and in the later stage,HBxAg may induce immune escape by up-regulating Fas-L expression in liver cells.Together,HBxAg and high HBV DNA load may promote chronic HBV infection and progression to hepatocarcinogenesis.