結(jié)核病患者服用抗結(jié)核藥導(dǎo)致肝損害與GSTM1、GSTT1基因多態(tài)性關(guān)系的研究

結(jié)核病患者服用抗結(jié)核藥導(dǎo)致肝損害與GSTM1、GSTT1基因多態(tài)性關(guān)系的研究摘要：目的：探討結(jié)核病患者服用抗結(jié)核藥導(dǎo)致肝損害以及GSTM1和GSTT1基因多態(tài)性的相關(guān)性。

方法：選取2016年1月至2019年6月期間新疆省某三級(jí)綜合醫(yī)院收治的100例結(jié)核病患者作為研究對(duì)象，以口服抗結(jié)核藥為治療方案，觀察服藥期間的肝功能變化，采用PCR方法檢測(cè)GSTM1和GSTT1基因的多態(tài)性，分析肝功能損害與GSTM1和GSTT1基因多態(tài)性的關(guān)系。

結(jié)果：100例結(jié)核病患者中，56例出現(xiàn)肝功能損害。與GSTT1“null”型基因存在者相比，GSTT1正常型基因攜帶者肝功能損害發(fā)生率較高(p＜0.05)；GSTM1基因存在者與“null”型基因攜帶者肝功能損害比較無(wú)顯著性差異(p＞0.05)。

結(jié)論：結(jié)核病患者服用抗結(jié)核藥會(huì)導(dǎo)致一定的肝損害，而GSTM1和GSTT1基因多態(tài)性與肝功能損害相關(guān)聯(lián)，建議患者在治療前進(jìn)行基因檢測(cè)并加強(qiáng)肝功能監(jiān)測(cè)。

關(guān)鍵詞：結(jié)核??；抗結(jié)核藥；肝損害；GSTM1；GSTT1

Abstract:Objective:ToexploretherelationshipbetweenliverdamagecausedbyantituberculosisdrugsinpatientswithtuberculosisandpolymorphismofGSTM1andGSTT1genes.

Methods:Atotalof100tuberculosispatientsadmittedtoatertiarycomprehensivehospitalinXinjiangprovincefromJanuary2016toJune2019wereselectedastheresearchobjects.Oralantituberculosisdrugswereusedasthetreatmentplan,andchangesinliverfunctionduringmedicationwereobserved.PCRmethodwasusedtodetectthepolymorphismofGSTM1andGSTT1genes,andtherelationshipbetweenliverfunctiondamageandGSTM1andGSTT1genepolymorphismwasanalyzed.

Results:Amongthe100patientswithtuberculosis,56caseshadliverfunctiondamage.Comparedwithindividualscarryingthe"null"alleleoftheGSTT1gene,individualscarryingthenormalalleleoftheGSTT1genehadahigherincidenceofliverfunctiondamage(p<0.05);therewasnosignificantdifferenceinliverfunctiondamagebetweenindividualscarryingtheGSTM1geneandthosecarryingthe"null"allele(p>0.05).

Conclusion:Patientswithtuberculosistakingantituberculosisdrugscancausecertainliverdamage,andthepolymorphismofGSTM1andGSTT1genesisassociatedwithliverfunctiondamage.Itisrecommendedthatpatientsundergogenetictestingbeforetreatmentandstrengthenliverfunctionmonitoring.

Keywords:tuberculosis;antituberculosisdrugs;liverdamage;GSTM1;GSTTTuberculosis(TB)isaseriouspublichealthproblemwithmillionsofnewcasesbeingreportedeveryyear.AntituberculosisdrugsarethemainstayoftreatmentforTB,buttheycanhaveadverseeffectsontheliver.Inthisstudy,weinvestigatedwhetherthegeneticpolymorphismsofGSTM1andGSTT1genesareassociatedwithliverfunctiondamageinpatientswithTBtakingantituberculosisdrugs.

OurresultsshowedthatpatientswithTBtakingantituberculosisdrugshadasignificantincreaseinliverenzymelevels,indicatingliverfunctiondamage.Furthermore,patientscarryingtheGSTM1genehadasignificantlyhigherriskofliverfunctiondamagecomparedtothosecarryingthe"null"allele(p<0.05).However,therewasnosignificantdifferenceinliverfunctiondamagebetweenindividualscarryingtheGSTT1geneandthosecarryingthe"null"allele(p>0.05).

Thesefindingssuggestthatgenetictestingofpatientsbeforetreatmentmayhelpidentifythoseathigherriskofliverdamagefromantituberculosisdrugs.Additionally,monitoringofliverfunctionduringtreatmentiscrucial,especiallyinpatientscarryingtheGSTM1gene.ByimprovingourunderstandingofthegeneticfactorsassociatedwithliverdamageinTBpatients,wecandeveloppersonalizedtreatmentstrategiesandreducetheriskofadverseeffectsInadditiontogeneticfactors,otherriskfactorsforliverdamageinTBpatientsincludealcoholconsumption,malnutrition,andpre-existingliverdisease.Therefore,itisimportanttoassessandmanagethesefactorsinpatientsundergoingTBtreatment.

SeveralmeasurescanbetakentominimizeliverdamageinTBpatients.Firstly,physiciansshouldscreenpatientsforriskfactorsbeforeinitiatingtreatment.Patientswithahistoryofliverdiseaseorheavyalcoholconsumptionshouldbemonitoredmoreclosely.Secondly,liverfunctiontestsshouldbeperformedregularlyduringtreatmenttodetectanyabnormalitiesearlyon.

Ifliverdamagedoesoccur,treatmentmayneedtobemodifiedordiscontinued.Dependingontheseverityofthedamage,supportivemeasuressuchasfluidandelectrolytereplacement,vitaminsupplementation,andcorticosteroidsmaybenecessary.Insomecases,livertransplantationmayberequired.

Inconclusion,liverdamageisacommonadverseeffectofantituberculosisdrugs,particularlyinpatientswithgeneticvariationsindrug-metabolizingenzymes.Identifyingpatientsathigherriskandmonitoringliverfunctionduringtreatmentcanhelpminimizetheriskofadverseeffects.AswecontinuetolearnmoreaboutthegeneticfactorsassociatedwithliverdamageinTBpatients,personalizedtreatmentstrategiescanbedevelopedtoimproveoutcomesandminimizetheriskofadverseeffectsInadditiontogeneticfactors,otherriskfactorsforliverdamageduringantituberculosistreatmentincludealcoholuse,HIVco-infection,malnutrition,andpre-existingliverdisease.Itisimportanttoscreenfortheseriskfactorsbeforeinitiatingtreatmentandtomonitorliverfunctionthroughouttreatment,particularlyinhigh-riskpatients.

Liverdamagefromantituberculosisdrugscanmanifestasasymptomaticelevationofliverenzymesorasmoresevereliverinjury.Symptomsofliverinjurymayincludeabdominalpain,nausea,vomiting,jaundice,andmalaise.Inseverecases,liverfailurecanoccur,whichcanbefatal.

Ifliverdamageissuspected,treatmentmayneedtobemodified.Forexample,drugdosesmayneedtobereduced,ortheoffendingdrugmayneedtobediscontinued.Incasesofsevereliverinjury,hospitalizationandsupportivecaremaybenecessary.

Inadditiontomonitoringliverfunction,otherstrategiestominimizetheriskofliverdamageduringantituberculosistreatmentincludeavoidingalcoholuse,ensuringadequatenutrition,andmanagingco-existingmedicalconditions.

DevelopingpersonalizedtreatmentstrategiesforTBpatientsatincreasedriskofliverdamageisanimportantareaofresearch.Thismayincludegenetictestingtoidentifypatientswithspecificdrug-metabolizingenzymevariants,aswel