血清乙型肝炎病毒-DNA载量对乙型肝炎患者肝功能及外周血内质网应激相关指标的影响研究

Effect of Serum HBV-DNA Load on Liver Function and Endoplasmic Reticulum Stress in Peripheral Blood in Patients with Hepatitis B

目的分析血清乙型肝炎病毒(HBV)-DNA载量对乙型肝炎(以下简称乙肝)患者肝功能及外周血内质网应激(ERS)相关指标的影响,为乙肝的临床诊治提供依据。方法选取2016年7月—2017年6月在唐山市传染病医院治疗的乙肝患者136例。按血清HBV-DNA载量将患者分为阴性组(血清HBV-DNA载量<1.0×10~3 copies/ml)、低拷贝组(1.0×10~3 copies/ml≤血清HBV-DNA载量<1.0×10~5 copies/ml)、中拷贝组(1.0×10~5 copies/ml≤血清HBV-DNA载量<1.0×10~7 copies/ml)、高拷贝组(血清HBV-DNA载量≥1.0×10~7 copies/ml)。同期选取在唐山市传染病医院治疗的非HBV感染患者82例为对照组。检测并比较5组血清HBV-DNA载量、肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(γ-GT)、碱性磷酸酶(ALP)]、ERS相关指标[葡萄糖调节蛋白78(GRP78)、CCAAT/增强子结合蛋白(CHOP)、天冬半胱氨酸特异性蛋白酶-12(caspase-12)],分析肝功能指标与血清HBV-DNA载量及ERS相关指标的相关性。结果 5组ALP比较,差异无统计学意义(P>0.05);低拷贝组、中拷贝组、高拷贝组ALT、AST高于对照组、阴性组(P<0.05);中拷贝组、高拷贝组ALT、AST高于低拷贝组(P<0.05);高拷贝组ALT、AST高于中拷贝组(P<0.05);阴性组、低拷贝组、中拷贝组、高拷贝组γ-GT高于对照组(P<0.05)。阴性组、低拷贝组、中拷贝组、高拷贝组GRP78、CHOP、caspase-12高于对照组(P<0.05);低拷贝组GRP78低于阴性组(P<0.05);中拷贝组GRP78高于低拷贝组(P<0.05)。ALT、AST与血清HBV-DNA载量均呈正相关(P<0.05);γ-GT、ALP与血清HBV-DNA载量无直线相关关系(P>0.05)。ALT、AST、γ-GT、ALP与GRP78、CHOP、caspase-12均无直线相关关系(P>0.05)。结论乙肝患者血清HBV-DNA载量可对肝功能产生影响,且可诱发外周血ERS,这对乙肝的发病机制研究及临床诊治有一定的现实指导意义。

Objective To analyze the effect of serum hepatitis B virus(HBV)-DNA load on liver function and endoplasmic reticulum stress(ERS)in peripheral blood in patients with hepatitis B,so as to provide evidence for clinical diagnosis and treatment of HBV.Methods A total of 136 cases of patients with hepatitis B admitted to Tangshan Infectious Disease Hospital from July 2016 to June 2017 were enrolled and were divided into negative group(serum HBV-DNA load<1.0×103 copies/ml),low copy group(1.0×103 copies/ml≤Serum HBV-DNA load<1.0×105 copies/ml),medium copy group(1.0×105 copies/ml≤Serum HBV-DNA load<1.0×107 copies/ml),and high copy group(serum HBV-DNA load≥1.0×107 copies/ml).A total of 82 non-HBV infection patients admitted to Tangshan Infectious Disease Hospital were selected as the control group.Serum HBV-DNA load,liver function indexes〔alanine aminotransferase(ALT),aspartic acid aminotransferase(AST),Gamma transglutaminase(γ-GT),alkaline phosphatase(ALP)〕,ERS-related indexes〔glucose regulation protein(GRP78),CCAAT/-enhanced protein(CHOP)and cysteine aspartyl-specific protease-12(caspase-12)〕were detected and compared in 5 groups.The correlation of liver function index with serum HBV-DNA load and ERS-related indexes was analyzed.Results There was no significant difference in ALP in 5 groups(P>0.05).ALT and AST in low copy group,medium copy group and high copy group were higher than those in control group and negative group(P<0.05).ALT and AST in medium copy group and high copy group were higher than those in low copy group(P<0.05).ALT and AST in high copy group were higher than those in medium copy group(P<0.05).γ-GT in negative group,low copy group,medium copy group and high copy group was higher than that in the control group(P<0.05).GRP78,CHOP,caspase-12 in negative group,low copy group,medium copy group and high copy group were higher than those in control group(P<0.05).GRP78 in low copy group was lower than that in negative group(P<0.05),and GRP78 in medium copy group was higher than that in low copy group(P<0.05).ALT and AST were positively correlated with serum HBV-DNA load(P<0.05),γ-GT and ALP had no linear correlation with serum HBV-DNA load(P>0.05).There was no linear correlation between ALT,AST,γ-GT,ALP and GRP78,CHOP and caspase-12(P>0.05).Conclusion The serum HBV-DNA load in patients with hepatitis B can affect the liver function and induce ERS in peripheral blood,which has a certain practical guiding significance for pathogenesis,clinical diagnosis and treatment of hepatitis B.