CAJ | 학술논문

目的：探讨慢性HBV感染者高尔基体蛋白73（GP73）水平与肝脏炎症损伤的相关性。方法收集慢性HBV感染者573例，其中慢性乙型肝炎（CHB）轻度患者107例、中度患者191例和重度患者132例，HBV相关的慢加急性和慢加亚急性肝功能衰竭（ACLF）患者50例和失代偿期乙型肝炎肝硬化（HLC）患者93例。采用ELISA法检测血清GP73，采用免疫组织化学技术检测肝组织GP73表达，并对血清GP73水平与慢性HBV感染者疾病进展的相关性进行分析。结果血清GP73水平在轻度CHB、中度CHB、重度CHB、HLC和ACLF中持续升高，分别为（71.54±39.48）ng/ml、（143.70±70.16）ng/ml、（218.20±79.34）ng/ml、（244.67±83.36）ng/ml和（275.61±104.05）ng/ml，各组血清GP73水平差异均有统计学意义（P均＜0.05）。血清GP73水平与慢性HBV感染者病情进展呈正相关关系（r=0.723，P＜0.0001）。HBeAg阳性与HBeAg阴性CHB患者比较，血清GP73水平差异无统计学意义（t=1.966，P＞0.05）。在不同血清HBV DNA含量之间比较，患者血清GP73水平差异无统计学意义（F=1.220，P＞0.05）。血清GP73水平随着血清白蛋白（ALB）含量的下降而逐渐升高，随着血清总胆红素（TBil）、丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）含量的升高而逐渐升高，血清GP73水平与ALB（r=－0.573，P＜0.0001）含量呈负相关关系，与TBil（r=0.623，P＜0.0001）、ALT（r=0.521，P＜0.0001）以及AST（r=0.542，P＜0.0001）含量均呈正相关关系。免疫组织化学染色分析结果显示，GP73主要在肝细胞浆内表达，在肝组织内浸润的炎症细胞和纤维隔中无表达。肝组织GP73表达随着病情从轻度、中度、重度CHB到HLC的进展逐渐增强，与轻度CHB对比，重度CHB和HLC患者肝组织GP73呈强阳性表达。结论血清GP73水平与慢性HBV感染者肝脏炎症损伤密切相关，与HBV复制水平无关。血清GP73可作为评估肝脏炎症损伤的一个重要标志。目的：探討慢性HBV感染者高爾基體蛋白73（GP73）水平與肝髒炎癥損傷的相關性。方法收集慢性HBV感染者573例，其中慢性乙型肝炎（CHB）輕度患者107例、中度患者191例和重度患者132例，HBV相關的慢加急性和慢加亞急性肝功能衰竭（ACLF）患者50例和失代償期乙型肝炎肝硬化（HLC）患者93例。採用ELISA法檢測血清GP73，採用免疫組織化學技術檢測肝組織GP73錶達，併對血清GP73水平與慢性HBV感染者疾病進展的相關性進行分析。結果血清GP73水平在輕度CHB、中度CHB、重度CHB、HLC和ACLF中持續升高，分彆為（71.54±39.48）ng/ml、（143.70±70.16）ng/ml、（218.20±79.34）ng/ml、（244.67±83.36）ng/ml和（275.61±104.05）ng/ml，各組血清GP73水平差異均有統計學意義（P均＜0.05）。血清GP73水平與慢性HBV感染者病情進展呈正相關關繫（r=0.723，P＜0.0001）。HBeAg暘性與HBeAg陰性CHB患者比較，血清GP73水平差異無統計學意義（t=1.966，P＞0.05）。在不同血清HBV DNA含量之間比較，患者血清GP73水平差異無統計學意義（F=1.220，P＞0.05）。血清GP73水平隨著血清白蛋白（ALB）含量的下降而逐漸升高，隨著血清總膽紅素（TBil）、丙氨痠氨基轉移酶（ALT）和天門鼕氨痠氨基轉移酶（AST）含量的升高而逐漸升高，血清GP73水平與ALB（r=－0.573，P＜0.0001）含量呈負相關關繫，與TBil（r=0.623，P＜0.0001）、ALT（r=0.521，P＜0.0001）以及AST（r=0.542，P＜0.0001）含量均呈正相關關繫。免疫組織化學染色分析結果顯示，GP73主要在肝細胞漿內錶達，在肝組織內浸潤的炎癥細胞和纖維隔中無錶達。肝組織GP73錶達隨著病情從輕度、中度、重度CHB到HLC的進展逐漸增彊，與輕度CHB對比，重度CHB和HLC患者肝組織GP73呈彊暘性錶達。結論血清GP73水平與慢性HBV感染者肝髒炎癥損傷密切相關，與HBV複製水平無關。血清GP73可作為評估肝髒炎癥損傷的一箇重要標誌。
목적：탐토만성HBV감염자고이기체단백73（GP73）수평여간장염증손상적상관성。방법수집만성HBV감염자573례，기중만성을형간염（CHB）경도환자107례、중도환자191례화중도환자132례，HBV상관적만가급성화만가아급성간공능쇠갈（ACLF）환자50례화실대상기을형간염간경화（HLC）환자93례。채용ELISA법검측혈청GP73，채용면역조직화학기술검측간조직GP73표체，병대혈청GP73수평여만성HBV감염자질병진전적상관성진행분석。결과혈청GP73수평재경도CHB、중도CHB、중도CHB、HLC화ACLF중지속승고，분별위（71.54±39.48）ng/ml、（143.70±70.16）ng/ml、（218.20±79.34）ng/ml、（244.67±83.36）ng/ml화（275.61±104.05）ng/ml，각조혈청GP73수평차이균유통계학의의（P균＜0.05）。혈청GP73수평여만성HBV감염자병정진전정정상관관계（r=0.723，P＜0.0001）。HBeAg양성여HBeAg음성CHB환자비교，혈청GP73수평차이무통계학의의（t=1.966，P＞0.05）。재불동혈청HBV DNA함량지간비교，환자혈청GP73수평차이무통계학의의（F=1.220，P＞0.05）。혈청GP73수평수착혈청백단백（ALB）함량적하강이축점승고，수착혈청총담홍소（TBil）、병안산안기전이매（ALT）화천문동안산안기전이매（AST）함량적승고이축점승고，혈청GP73수평여ALB（r=－0.573，P＜0.0001）함량정부상관관계，여TBil（r=0.623，P＜0.0001）、ALT（r=0.521，P＜0.0001）이급AST（r=0.542，P＜0.0001）함량균정정상관관계。면역조직화학염색분석결과현시，GP73주요재간세포장내표체，재간조직내침윤적염증세포화섬유격중무표체。간조직GP73표체수착병정종경도、중도、중도CHB도HLC적진전축점증강，여경도CHB대비，중도CHB화HLC환자간조직GP73정강양성표체。결론혈청GP73수평여만성HBV감염자간장염증손상밀절상관，여HBV복제수평무관。혈청GP73가작위평고간장염증손상적일개중요표지。
Objective To explore the correlation between level of Golgi protein 73 (GP73) and liver inflammatory injury in patients with chronic hepatitis B virus (HBV) infection. Methods Total of 573 paitients with chronic HBV infection were enrolled, including 107 cases with mild chronic hepatitis B (CHB), 191 cases with moderate CHB, 132 cases with severe CHB, 50 cases with HBV related acute on chronic and subacute on chronic liver failure (ACLF) and 93 cases with decompensate hepatitis B liver cirrhosis (HLC). The serum GP73 were meaured by ELISA, and the GP73 expression in liver tissues were detected by immunohistochemistry. The correlation between GP73 and the progression in patients with chronic HBV infection were analyzed, respectively. Results The level of serum GP73 showed a continuous increase among patients with mild CHB (71.54 ± 39.48 ng/ml), moderate CHB (143.70 ± 70.16 ng/ml) and severe CHB (218.20 ± 79.34 ng/ml), HLC (244.67 ± 83.36 ng/ml) and ACLF (275.61 ± 104.05 ng/ml), and there were signiifcant differences in the levels of serum GP73 among all the groups (P all<0.05). The level of serum GP73 was positively correlated with disease progression in chronic HBV infection (r = 0.723, P<0.0001). HBeAg positive and HBeAg negative CHB were compared, the serum GP73 level was with no signiifcant difference (t=1.966, P>0.05). The different contents of serum HBV DNA were compared the serum GP73 level was with no signiifcant difference (F=1.220, P>0.05). The level of serum GP73 signiifcantly increased with the reduction of the albumin (ALB) level, and increased with the elevation of levels of the total bilirubin (TBil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The serum GP73 level negatively correlated with the level of ALB (r=-0.573, P<0.0001), and positively correlated with the level of TBil (r=0.623, P<0.0001), ALT (r=0.521, P<0.0001) and AST (r=0.542, P<0.0001). Immunohistochemical staining analysis showed that GP73 expression was found in the cytoplasm of hepatocytes, but not in the inifltrating inlfammatory cells or in cells within the ifbrotic septa. The expression of GP73 increased gradually with the progression from mild, moderate and severe CHB to HLC. Compared with mild CHB, GP73 were signiifcantly expressed in severe CHB and HLC. Conclusions The level of serum GP73 are correlated with liver inlfammatory injury in patients with chronic HBV infection, and not associated with level of HBV replication. The level of serum GP73 might be an important marker to evaluate liver inlfammatory injury.