高敏PCR在HBV极低病毒载量的慢性乙型肝炎患者中检测的临床意义.docx
病毒性肝炎DOI:10.12449/JCH240308高敏PCR在HBV极低病毒载量的慢性乙型肝炎患者中检测的临床意义丘助钦/，谢丹瞰任小，欧阳Qa.b广州医科大学附属第五医院a.感染性疾病科，b.广东高校生物靶向诊治与康复重点实验室，广州510000阖言储：邸昭,ouyangshi(ORQD:0000-0003-0173-3276)摘要：目的探讨使用高敏PCR在HBV极例声毒载量(HBVDNAlO99IUmL)人群检测中的意义。方法选取2019年9月2022年2月三州医科大哪解五医献受螃(酸)狗以物(NAs)治疗N48周敏HBVDNA*佥则(顾!1佛100IUmL)结果为低于检测下限的慢性乙型肝炎(CHB)患者，进一步行高敏HBVDNA检测(检测下限10IUmL),根据结果分为极低病毒载量(VLVL,HBVDNA1099ImL)组和完溺毒学应答(CVR,HBVDNA<10ImL或未检测到)组。比较两组患者的一般特征、血清病毒学指标、生化学指标、无创肝纤维化指标，评价相关血清病毒学指标对高敏HBVDNA高于检测下限的预测价值，并探讨未实现CVR的影响因素。符合正态分布的计量资料两组间比较采用成组f检验；非正态分布的计量资料两组间比较采用Mann-WhitneyU检验。计数资料两组间比较采用/检验或FiSher精确检验。采用受试者工作特征曲线(ROC曲线)评价相关血清病毒学指标对高敏HBVDNA高于检测下限的预测价值。采用二元Logistic回归分析探讨未实现CVR的影响因素。结果共纳入106例CHB患者，其中VLVL组24例、CVR组82例.VLVL组年龄小于CVR组(p=0.004)1VLVLqHBsAgzK三F(P=O.002)HBeAgB0»(P=。002)、PgRNAB(GQOlO)及ALT水平(P=OOl7)高于CVR组。qHBsAg水平预测CHB患者采用高敏HBVDNA检查结果高于检测下限(>10IUmL)的ROC曲线下面积为0.717(P=Q.002),最佳CUtQff值为1214.5IUmL,酸三度为95.5%,特异劭53.9%HBeAg阳性(OR=3.654,95%C:1.16211.489,P=O.027)和qHBsAg(0R=2.985,95%C:1.0588.422,P=O.039)嫌频CVR雌立影响因素.结论CHB患者经普敏检测HBVDNA低于<100IUmL酶高敏PCR检测实际仍存在VLVLVLVL患者炎症损伤水平、PgRNA阳性率以及HBeAg阳性率均显著高于CVR者oHBeAg阳性和高qHBsAg水平是CHB患者未实现CVR的独立影响因素。临床医师不应忽视CHB患者中VLVL人群，需及时行高敏HBVDNA检测。关键词：乙型肝炎，慢性；聚合酶链反应；极低病毒载量基金项目：国家自然科学基金(81803884)；广东高校生物靶向诊治与康复重点实验室(2021KSYS009)；广州市医学重点学科项目(20212023年)；本科生创新能力提升计划项目(2022JXAo03);广州医科大学科研能力提升项目(02-410-2302092XM);2022年广州阚:设项目(02-410-2206013);2023年视(院)企联日助项目(2023A03J0421);2023年北京肝胆相照公益基金会资助项目(iGandaF-1082023-RGG023)Significanceofhigh-sensitivitypolymerasechainreactionindetectinghepatitisBvirusinchronichepatitisBpatientswithaverylowviralloadQIUGongqiri'-b,XIEDarf,b,CHENZiren11b,OUYANGShPT(a.DepartmentOflnfectiousDiseases,b.KeyLaboratoryOfBioIogicaITargetingDiagnosis,TherapyandRehabilitationOfGuangdongHigherEducationInstitutes,Guangzhou510000,China)Correspondingauthor:OUYANGShi,ouyangshi(ORCID:0000-0003-0173-3276)Abstract:ObjectiveToinvestigatethesignificanceofhigh-sensitivepolymerasechainreaction(PCR)indetectinghepatitisBvirus(HBV)amongthepopulationwithaverylowviralload(HBVDNA1099IUmL).MethodsThisstudywascductedamongtechronichepatitisB(CHB)patientswhoweretreatedwithnudeos(t)ideanaloguesfor>48weeksinTheFifthAffiIiatedHospitalofGuangzhouMedicalUniversityfromSeptember2019toFebruary2022andhadanHBVDNAloadbelowthelowerlimitofordinary-sensitivitydetection(100IUmL).Thenhigh-sensitivityHBVDNAdetectionwasperformedforallpatients,andaccordingtotheseresults,thepatientsWeredividedintoVefylowviralloadgxp(VLVLgroupwithanHBVDNAloadf1099IUmL)andcompletevirdogicresponsegroup(CVRgroupwithanHBVDNAloadof<10IUmLorwithoutHBVDNAdetected).Thetwogroupswerecomparedintermsofgeneralcharacteristics,se11jmVirologicalindicators,biochemicalparameters,andnoninvasivefibrosismarkers;thevalueofrelatedserumVirologicalindicatorsinpredictingtheresultsofhigh-sensitivityHBVDNAabovethelowerlimitofdetectiwereassessed;theinfluencingfactorsforfailuretoachieveCVRwereanalyzed.Theindependent-samplesttestwasusedforcomparisofnormallydistributedcontinusdatabetweentwogroups,andtheMano-Whitneyt/testwasusedforcomparisonofnon-nomallydistributedcontinuousdatabetweentwogroups;thechi-squaretestortheFisher,Sexacttestwasusedforcomparisonofcategoricaldatabetweentwogrps.Thereceiveroperatingcharacteristic(ROC)curvewasusedtoinvestigatethevalueofrelatedsermVirologicalindicatorsinpredictingtheresultsofhigh-sensitivityHBVDNAabovethelowerlimitofdetection,andabinarylogisticregressionanalysiswasusedtoinvestigatetheinfluencingfactorsforfailuretoachieveCVR.ResultsAtotalof106CHBpatientswereenrolled,with24intheVLVLgroupand82intheCVRgroup.ComparedwiththeCVRgroup,theVLVLgrouphadasignificantlyyoungerage(P=O.004)andsignificantlyhigherquantitativehepatitisBsurfaceantigen(qHBsAg)level(P=0.002),HBeAgpositiverate(P=0.002),pgRNApositiverate(P=0.010),andalanineaminotransferaselevel(P=0.017).TheqHBsAglevelhadanareaundertheROCcurveof0.717(P=0.002)inpredictingtheresultsofhigh-sensitivityHBVDNAabovethelowerlimitofdetection(>10IUmL),withanoptimalcut-offvalueof1214.5IUmL,asensitivityof95.5%,andaSPeCifidtyof53.9%.PositiveHBeAg(oddsratioOR=3.654,95%confidenceintervalCl:1.16211489,P=0.027)andqHBsAg(OR=2.985,95%C:10588.422,P=O.039)wereindependentinfluencingfactorsforfailuretoachieveCVR.ConclusionSomeCHBpatientshaveanHBVDNAloadof<100IUmLbyordinary-sensitivitydetection,butwiththepresenceofVLVLdeterminedbyhigh-sensitivityPCR.TheVLVLgrouphadsignificantlyhigherlevelofinflammatorydamageandpositiveratesofpgRNAandHBeAg.PositiveHBeAgandhighqHBsAglevelareindependentinfluencingfectorsforfailuretoachieveCVR.GinidansshouldnotignorethepresenceofVLVLinCHBpatients,andhigh-sensitivityHBVDNAdetectionshouldbeperformedinatimelymanner.Keywords:HepatitisB,Chronic;PolymeraseChainReaction;VeryLowViralLoadResearchfunding:NationalNaturalScienceFoUndationofChina(81803884);TheKeyLaboratoryofGuangdongHigherEducationInstitutes(2021KSYS009);TbeKeyMedicalDisciplinesofGuangzhouProject(20212023);UndergraduateInnovationAbilityEnhancementProgramProject(2
