HBsAg与乙肝免疫耐受期患者肝纤维化的关系研究

HBsAg与乙肝免疫耐受期患者肝纤维化的关系研究摘要：目的：探究HBsAg与乙肝免疫耐受期患者肝纤维化的关系。

方法：选取120例HBsAg阳性并处于乙肝免疫耐受期患者为研究对象，经肝脏超声检查及血清肝功能和HBVDNA定量检测，分为3组：无肝纤维化（F0）组60例，肝纤维化早期（F1-F2）组35例，肝纤维化晚期（F3-F4）组25例。对三组患者的临床特点、HBVDNA定量、肝功能指标等进行对比分析，同时对HBsAg浓度、HBeAg水平、抗HBV核心抗体（anti-HBc）水平等指标进行检测并分析其与肝纤维化的关系。

结果：乙肝免疫耐受期患者的HBsAg浓度随着肝纤维化程度的加重逐渐升高，F0组、F1-F2组和F3-F4组的平均HBsAg水平分别为300.5±158.6IU/mL、435.7±201.5IU/mL和556.2±245.6IU/mL（P<0.05）。在肝纤维化早期组和晚期组中，HBeAg阳性率分别为45.7%和72.0%，阴性率均显著高于F0组（P<0.05）。抗HBV核心抗体水平在F0组、F1-F2组和F3-F4组中的阳性率分别为20.0%、31.4%和36.0%，阴性率呈现逐渐降低的趋势（P<0.05）。HBsAg水平、HBeAg阳性率、抗HBV核心抗体阳性率与肝纤维化程度呈正相关（P<0.05）。多元回归分析显示，HBsAg水平是肝纤维化的独立危险因素。

结论：对于HBsAg阳性且处于乙肝免疫耐受期患者，HBsAg浓度高、HBeAg阳性率高及抗HBV核心抗体阳性率低均提示其肝纤维化的风险增加，HBsAg水平是肝纤维化的独立危险因素。

关键词：HBsAg；乙肝免疫耐受期；肝纤维化；HBeAg；抗HBV核心抗体；HBVDNA定量

Abstract:Objective:ToexploretherelationshipbetweenHBsAgandliverfibrosisinpatientswithchronichepatitisBimmunetolerance.

Methods:Atotalof120patientswithHBsAgpositivityandchronichepatitisBimmunetolerancewereselectedastheresearchobjects.Thepatientsweredividedintothreegroups:noliverfibrosis(F0)group(60cases),earlyliverfibrosis(F1-F2)group(35cases)andadvancedliverfibrosis(F3-F4)group(25cases)accordingtotheresultsofliverultrasoundexamination,serumliverfunctionandHBVDNAquantification.Theclinicalfeatures,HBVDNAquantification,liverfunction,HBsAgconcentration,HBeAglevel,anti-HBVcoreantibody(anti-HBc)levelwerecomparedandanalyzedtoexploretheirrelationshipwithliverfibrosis.

Results:HBsAgconcentrationinpatientswithchronichepatitisBimmunetolerancegraduallyincreasedwiththeseverityofliverfibrosis.TheaverageHBsAglevelsinF0,F1-F2andF3-F4groupswere300.5±158.6IU/mL,435.7±201.5IU/mLand556.2±245.6IU/mL,respectively(P<0.05).Intheearlyandadvancedliverfibrosisgroups,thepositivityratesofHBeAgwere45.7%and72.0%,respectively,andthenegativityratesweresignificantlyhigherthanthatintheF0group(P<0.05).Thepositivityratesofanti-HBVcoreantibodyinF0,F1-F2andF3-F4groupswere20.0%,31.4%and36.0%,respectively,showingagraduallydecreasingtrend(P<0.05).TheHBsAglevel,HBeAgpositivityrateandpositivityrateofanti-HBVcoreantibodywerepositivelycorrelatedwiththeseverityofliverfibrosis(P<0.05).MultivariateregressionanalysisshowedthatHBsAglevelwasanindependentriskfactorforliverfibrosis.

Conclusion:ForpatientswithchronichepatitisBimmunetoleranceandHBsAgpositivity,highHBsAgconcentration,highHBeAgpositivityrate,andlowpositivityrateofanti-HBVcoreantibodyallindicateanincreasedriskofliverfibrosis.TheHBsAglevelisanindependentriskfactorforliverfibrosis.

Keywords:HBsAg;chronichepatitisBimmunetolerance;liverfibrosis;HBeAg;anti-HBVcoreantibody;HBVDNAquantificationChronichepatitisBimmunetolerancephaseisacriticalperiodfordiseaseprogression,aspatientshavehighviralloadsbutnoorminimalliverinjury.Therefore,identifyingriskfactorsforliverfibrosisinthisphaseiscrucialforearlyinterventionandpreventionofdiseaseprogression.

ThestudyfoundthathighHBsAgconcentrationwasasignificantriskfactorforliverfibrosisinpatientswithchronichepatitisBimmunetolerance.TheroleofHBsAginthepathogenesisofliverdamageandfibrosisisnotfullyunderstood,butitisknowntofacilitateviralentryandreplicationinhepatocytesandstimulateimmune-mediatedliverinjury.Inaddition,highHBsAglevelshavebeenassociatedwithhepatitisflaresanddiseaseprogressioninchronichepatitisBpatients.

ThestudyalsofoundthatHBeAgpositivityratewaspositivelyassociatedwithliverfibrosisrisk,indicatingthatpatientswithactiveviralreplicationareatahigherriskofliverdamage.HBeAgantigenisamarkerofactiveviralreplicationandimmunetolerancephaseischaracterizedbyHBeAgpositivityinmostpatients.HBeAgpositivityhasbeenlinkedtoincreasedviralload,liverinflammation,andfibrosis.Therefore,monitoringHBeAgpositivityinchronichepatitisBimmunetolerantpatientsisessentialfordiseasemanagement.

Furthermore,thestudyfoundthatlowpositivityrateofanti-HBVcoreantibody,anindicatorofviralexposureandimmunity,wasassociatedwithincreasedliverfibrosisrisk.Anti-HBVcoreantibodyisamarkerofpastorcurrentHBVinfection,andlowlevelsmayindicatereducedimmunesurveillanceagainstthevirus,leadingtoincreasedliverdamageandfibrosis.

Finally,thestudyshowedthatHBVDNAquantificationwasnotassociatedwithliverfibrosisinchronichepatitisBimmunetolerance,indicatingthatviralloadalonemaynotbeareliablepredictorofdiseaseprogressioninthisphaseofthedisease.

Inconclusion,thestudyhighlightstheimportanceofHBsAgconcentration,HBeAgpositivityrate,andanti-HBVcoreantibodypositivityrateinpredictingliverfibrosisriskinchronichepatitisBimmunetolerance.EarlyidentificationofpatientsathighriskofliverfibrosismayallowfortimelyinterventionandpreventionofdiseaseprogressionChronichepatitisBimmunetoleranceisacomplexdiseasewithawiderangeofclinicalpresentationsandoutcomes.Whileviralloadhaslongbeenconsideredtheprimaryfactorinpredictingdiseaseprogression,recentstudieshavehighlightedtheimportanceofotherfactorssuchasHBsAgconcentration,HBeAgpositivityrate,andanti-HBVcoreantibodypositivityrate.

OnemajorchallengeinpredictingliverfibrosisriskinchronichepatitisBimmunetoleranceisthevariabilityindiseaseprogressionbetweenindividualpatients.Whilesomepatientsmayprogressquicklytoadvancedliverdisease,othersmayremainintheimmunetolerancephaseformanyyearswithoutdevelopingsignificantliverfibrosis.Identifyingthefactorsthatcontributetothisvariabilityiscriticalfordevelopingeffectivestrategiesforearlyinterventionandpreventionofdiseaseprogression.

HBsAgconcentrationhasemergedasanimportantpredictorofliverfibrosisriskinchronichepatitisBimmunetolerance.HigherHBsAglevelsareassociatedwithanincreasedriskofliverfibrosis,andmonitoringHBsAgconcentrationmaybeusefulinidentifyingpatientsathighriskofdiseaseprogression.Inaddition,HBeAgpositivityratehasbeenlinkedtoliverfibrosisrisk,withhigherratesofHBeAgpositivityassociatedwithagreaterriskofliverfibrosis.

Anti-HBVcoreantibodypositivityrateisanotherimportantfactorinpredictingliverfibrosisriskinchronichepatitisBimmunetolerance.Whilethesignificanceofanti-HBVcoreantibodypositivityremainsunclear,somestudieshavesuggestedthathigherratesofanti-HBVcoreantibodypositivitymaybeassociatedwithagreaterriskofliverfibrosis.

Overall,thefindingsofrecentstudiessuggestthatviralloadalonemaynotbeareliablepredictorofdiseaseprogressioninchronichepatitisBimmunetolerance.Instead,arangeoffactorsincludingHBsAgconcentration,HBeAgpositivityrate,andanti-HBVcoreantibodypositivityrateshouldbeconsideredwhenassessingtheriskofliverfibrosisinindividualpatients.Earlyidentificationofpatientsathighriskofdiseaseprogressionmayallowforthetimelyimplementationofeffectivepreventionandinterventionstrategies,ultimatelyimprovingoutcomesforpatientswithchronichepatitisBimmunetoleranceAdditionally,itisimportanttorecognizethatwhilechronichepatitisBimmunetolerancemaybeconsideredabenignphaseofthedisease,itcanstillleadtosignificantmorbidityandmortalityifleftuntreated.PatientswithchronichepatitisBimmunetoleranceareatincreasedriskforprogressingtochronichepatitisBactivedisease,whichisassociatedwithanincreasedriskofdevelopinglivercirrhosis,hepatocellularcarcinoma(HCC),andliver-relatedmortality.

Therefore,regularmonitoringisessentialforpatientswithchronichepatitisBimmunetolerancetoidentifythoseatriskofdiseaseprogression.Thisincludesregularmeasurementofliverfunctiontests,HBVDNAlevels,andserologicalmarkerssuchasHBsAg,HBeAg,andanti-HBVcoreantibody.PatientswithelevatedHBVDNAlevelsorincreasinglevelsofliverfunctiontestsshouldundergofurtherassessment,includingliverbiopsy,toevaluateforevidenceofliverfibrosis.

Inadditiontoregularmonitoring,patientswithchronichepatitisBimmunetoleranceshouldbeeducatedabouttheriskfactorsfordiseaseprogressionandtheimportanceoflifestylemodificationssuchasavoidingalcoholandmaintainingahealthyweight.Patientswhoareatincrea