摘要
目的探讨细胞周期激酶抑制因子4基因座中反义非编码RNA(ANRIL)、微小RNA-122(miR-122)在隐匿性乙型肝炎病毒(HBV)感染鉴别诊断中的应用价值。方法选取2019年2月至2021年1月宁夏医科大学总医院感染科收治的20例隐匿性乙型肝炎患者为隐匿性乙型肝炎组;选取同期住院治疗的80例慢性乙型肝炎患者作为慢性乙型肝炎组;另同期选取80例健康体检者作为健康对照组。采用实时荧光定量PCR(qRT-PCR)法检测血清ANRIL、miR-122水平,PCR结合荧光探针的体外DNA扩增技术检测血清HBV DNA载量,全自动生化分析仪检测血清总胆红素(TBil)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平;分析隐匿性乙型肝炎患者血清ANRIL、miR-122与TBil、ALT、AST、HBV DNA载量的相关性;分析血清ANRIL、miR-122鉴别诊断隐匿性乙型肝炎的价值;分析影响隐匿性乙型肝炎发生的因素。结果慢性乙型肝炎组ANRIL、TBil[(42.94±7.85)mol/L]、ALT[(236.48±40.76)U/L]、AST[(193.26±45.78)U/L]水平高于隐匿性乙型肝炎组[(25.64±6.35)mol/L、(32.74±7.15)U/L、(29.36±7.24)U/L]和健康对照组[(22.46±4.68)mol/L、(26.95±7.03)U/L、(19.46±6.13)U/L],HBV DNA载量高于隐匿性乙型肝炎组[(6243.58±1006.74)VS(3.95±1.09)],miR-122(0.43±0.12)低于隐匿性乙型肝炎组(0.69±0.21)和健康对照组(1.02±0.23)(P<0.05);隐匿性乙型肝炎组(1.53±0.37)血清ANRIL高于健康对照组(1.01±0.21),miR-122低于健康对照组(P<0.05)。隐匿性乙型肝炎患者血清ANRIL与miR-122呈负相关(r=-0.597,P<0.05),且ANRIL(miR-122)与TBil、ALT、AST、HBV DNA载量均呈正(负)相关(P<0.05)。血清ANRIL、miR-122及二者联合鉴别诊断隐匿性乙型肝炎的曲线下面积(AUC)分别为0.901、0.887、0.941,特异度分别为91.2%、73.8%、96.3%,敏感度分别为85.0%、95.0%、90.0%。ANRIL是影响隐匿性乙型肝炎发生的独立危险因素(P<0.05),miR-122是影响隐匿性乙型肝炎发生的保护因素(P<0.05)。结论隐匿性乙型肝炎患者血清ANRIL表达水平升高,miR-122表达水平降低,二者对鉴别诊断隐匿性乙型肝炎有良好的特异度和敏感度。
Objective To explore the application value of antisense noncoding RNA in cyclin kinase inhibitor 4 locus(ANRIL)and microRNA-122(miR-122)in the differential diagnosis of occult hepatitis B virus(HBV)infection.Methods Twenty patients with occult hepatitis B admitted from February 2019 to January 2021 were selected as occult hepatitis B group.Eighty patients with chronic hepatitis B hospitalized at the same period of time were selected as chronic hepatitis B group.Eighty healthy people were enrolled as the healthy control group.Serum samples were collected from all groups of people.The serum levels of ANRIL and miR-122 were detected by real-time fluorescence quantitative PCR(qRT-PCR).The serum HBV DNA load was detected by PCR in combination with fluorescence probe in vitro.The levels of serum total bilirubin(TBil),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected by automatic biochemical analyzer.The correlations between serum levels of ANRIL,miR-122,and TBIL,ALT,AST,and HBV DNA load in patients with occult hepatitis B were analyzed.The values of serum ANRIL and miR-122 in differential diagnosis of occult hepatitis B was analyzed.The influencing factors of occult hepatitis B were analyzed.Results The levels of TBIL,ALT,and AST in chronic hepatitis B group[(42.94±7.85)mol/L,(236.48±40.76)U/L,and(193.26±45.78)U/L,respectively]were higher than those in occult hepatitis B group[(25.64±6.35)mol/L,(32.74±7.15)U/L,and(29.36±7.24)U/L,respectively]and healthy control group[(22.46±4.68)mol/L,(26.95±7.03)U/L,and(19.46±6.13)U/L,respectively].HBV DNA load in chronic hepatitis B group was higher than that in occult hepatitis B group[(6243.58±1006.74)vs(3.95±1.09)].The miR-122 level in chronic hepatitis B group(0.43±0.12)was lower than that in occult hepatitis B group(0.69±0.21)and healthy control group(1.02±0.23)(P<0.05).The serum ANRIL level of occult hepatitis B group(1.53±0.37)was higher than that of healthy control group(1.01±0.21),and the miR-122 level was lower than that of healthy control group(P<0.05).Serum ANRIL was negatively correlated with miR-122 in patients with occult hepatitis B(r=-0.597,P<0.05),and ANRIL(miR-122)was positively(negatively)correlated with TBIL,ALT,AST and HBV DNA load(P<0.05).The area under the curve(AUC)of serum ANRIL,miR-122 and their combination in the differential diagnosis of occult hepatitis B was 0.901,0.887 and 0.941,respectively;the specificity was 91.2%,73.8%and 96.3%,respectively;and the sensitivity was 85.0%,95.0%and 90.0%,respectively.ANRIL was an independent risk factor for occult hepatitis B(P<0.05),while miR-122 was a protective factor for occult hepatitis B(P<0.05).Conclusion The expression level of ANRIL is increased and the expression level of miR-122 is decreased in patients with occult hepatitis B.Both of them have good specificity and sensitivity in the differential diagnosis of occult hepatitis B.
作者
李想
王妍柏
王银锋
黄学兰
LI Xiang;WANG Yan-bai;WANG Yin-feng;HUANG Xue-lan(Medical Experimental Center,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Department of Neurology,General Hospital of Ningxia Medical University,Yinchuan 750004,China)
出处
《肝脏》
2022年第3期305-310,共6页
Chinese Hepatology
基金
宁夏自然科学基金项目(NZ16268)
宁夏医科大学校级重点项目(XZ2019007)。