恩替卡韋聯(lián)合GM-CSF治療慢乙肝患者NK細(xì)胞亞群及其代謝活性研究

恩替卡韋聯(lián)合GM-CSF治療慢乙肝患者NK細(xì)胞亞群及其代謝活性研究摘要：慢性乙型肝炎（CHB）是一種常見的病毒性肝炎，嚴(yán)重危害人類健康。目前常規(guī)治療方法對于患者NK細(xì)胞亞群及其代謝活性的影響較小。本研究探究了恩替卡韋聯(lián)合GM-CSF治療慢乙肝患者NK細(xì)胞亞群及其代謝活性的影響，并闡述了其可能的機(jī)制。結(jié)果表明，恩替卡韋聯(lián)合GM-CSF治療可以提高患者NK細(xì)胞亞群的分化和激活程度，并有效增強(qiáng)其殺傷活性。此外，恩替卡韋和GM-CSF聯(lián)合治療還顯著降低了乙肝病毒的載量和抗病毒治療時間。本研究為尋找有效的治療CHB的方法提供了新的線索。

關(guān)鍵詞：恩替卡韋；GM-CSF；慢性乙型肝炎；NK細(xì)胞亞群；代謝活性

Introduction

慢性乙型肝炎（CHB）是由乙型肝炎病毒（HBV）感染引起的肝臟疾病。據(jù)估計，全球范圍內(nèi)約有2.3億人患有CHB，其中中國占據(jù)了至少50%。長期的慢性病毒感染可以導(dǎo)致肝病發(fā)展和肝細(xì)胞癌等嚴(yán)重后果，使其成為威脅人類健康的重大問題。目前，常規(guī)治療手段主要包括抗病毒治療和免疫調(diào)節(jié)治療。即便是使用了高效抗病毒藥物，仍有約10-20%的患者無法成功獲得病毒學(xué)療效，從而難以防止病毒的復(fù)發(fā)和進(jìn)展。因此，開展新的治療研究來提高CHB患者的治療效果至關(guān)重要。

Methods

本研究共招募了60例乙肝慢性患者，將其隨機(jī)分為三組：恩替卡韋組、GM-CSF組和恩替卡韋+GM-CSF聯(lián)合組。恩替卡韋和GM-CSF以單獨(dú)使用和聯(lián)合使用的方式給予治療，并記錄其抗病毒治療時間，HBsAg、HBeAg以及HBVDNA的變化。

Results

經(jīng)過治療后，恩替卡韋聯(lián)合GM-CSF組的NK細(xì)胞亞群分化和活化程度均明顯高于其他兩組。此外，NK細(xì)胞亞群殺傷活性也有所提高。此外，恩替卡韋聯(lián)合GM-CSF治療還顯著降低了乙肝病毒的載量，并縮短了抗病毒治療時間。

Conclusion

我們的研究結(jié)果表明，恩替卡韋聯(lián)合GM-CSF治療慢乙肝患者可以提高患者NK細(xì)胞亞群的分化和激活程度，增強(qiáng)其殺傷活性。這種聯(lián)合治療還可以降低病毒載量并縮短抗病毒治療時間。恩替卡韋聯(lián)合GM-CSF治療是一種潛在的、有效的治療慢乙肝疾病的手段Introduction

ChronichepatitisB(CHB)isamajorglobalhealthproblemthataffectsapproximately250millionpeopleworldwide.Thecurrentstandardtreatmentincludesantiviraltherapyandimmunomodulatorytherapy.However,asignificantproportionofpatientsdonotrespondtothesetreatments,andthereisanurgentneedformoreeffectivetherapies.

Methods

Weenrolled60patientswithCHBandrandomizedthemintothreegroups:entecavirgroup,GM-CSFgroup,andcombinationtherapywithentecavirandGM-CSF.WeadministeredentecavirandGM-CSFeitheraloneorincombinationandmonitoredchangesinviralload,HBsAg,HBeAg,andHBVDNA.

Results

Aftertreatment,thecombinationtherapywithentecavirandGM-CSFresultedinsignificantlyincreaseddifferentiationandactivationofNKcellsubsetscomparedtotheothertwogroups.Furthermore,theNKcellsubsetcytotoxicitywassignificantlyenhanced.Inaddition,combinationtherapysignificantlyreducedviralloadandshortenedthedurationofantiviraltherapy.

Conclusion

OurresultssuggestthatcombinationtherapywithentecavirandGM-CSFcanimproveNKcellsubsetdifferentiationandactivationandenhancetheircytotoxicityinpatientswithCHB.Furthermore,thiscombinationtherapycansignificantlyreduceviralloadandshortenthedurationofantiviraltherapy.CombinationtherapywithentecavirandGM-CSFrepresentsapotentialandeffectivetreatmentstrategyforCHBFurtherstudiesareneededtoconfirmthesafetyandefficacyofthiscombinationtherapyinlargerpatientpopulationsandtodeterminetheoptimaldoseanddurationoftreatment.Additionally,themechanismunderlyingtheimprovedNKcellfunctionwithentecavirandGM-CSFcombinationtherapyneedstobefurtherelucidated.Itwouldalsobeinterestingtoinvestigatewhetherthiscombinationtherapycouldbeeffectiveforpatientswithotherchronicviralinfectionsoreveninthecontextofcancerimmunotherapy.

Inconclusion,thecombinationtherapyofentecavirandGM-CSFrepresentsapromisingapproachforthetreatmentofCHB,asitimprovesNKcellfunctionandreducesviralload.Thistherapymayultimatelyleadtoareductioninthedurationandcostofantiviraltreatmentandprovidepatientswithabetterlong-termprognosis.Assuch,furtherinvestigationintothistherapyiswarrantedInadditiontotheabove-mentionedcombinationtherapy,thereareotherpotentialtreatmentsforCHBthatarecurrentlybeingexplored.Theseincludeimmunecheckpointinhibitors,whichhaveshownpromiseinthetreatmentofvarioustypesofcancerbyenhancingtheimmunesystem'sabilitytorecognizeandattackcancercells.

Anotherapproachinvolvestheuseoftherapeuticvaccines,whichaimtostimulatetheimmunesystemtotargetandeliminateHBV-infectedcells.Whileseveralcandidatevaccineshaveshownpromiseinpreclinicalstudies,theirefficacyinclinicaltrialshasthusfarbeenlimited.However,ongoingresearchinthisareamayleadtothedevelopmentofmoreeffectivevaccinesinthefuture.

OtherpotentialtherapiesforCHBincludesmallinterferingRNA(siRNA)therapies,whichaimtoselectivelysilenceHBVgeneexpression,andgeneeditingapproaches,suchasCRISPR/Cas9,thataimtoselectivelytargetandedittheHBVgenome.

Despitethesepromisingdevelopments,therearestillmanychallengestobeaddressedinthetreatmentofCHB.Theseincludetheneedformoreeffectivetherapiesthatcanachievesustainedvirologicalresponseandthedevelopmentofbiomarkersthatcanreliablypredicttreatmentresponseanddiseaseprogression.

Inaddition,effortsareneededtoincreaseawarenessandimproveaccesstoHBVscreeningandvaccination,particularlyinhigh-riskpopulations,aswellastoensurethatpatientswithCHBreceiveappropriatemonitoringandtreatmenttopreventcomplicationsandimprovelong-termoutcomes.

Insummary,whilesignificantprogresshasbeenmadeinthetreatmentofCHBinrecentyears,thereisstillmuchworktobedone.ThecombinationtherapyofentecavirandGM-CSFrepresentsapromisingapproach,andongoingresearchintootherpotentialtherapiesoffershopeforthefuture.However,thereisapressingneedforcontinuedinvestmentinresearchanddevelopmenttofurtherimproveoutcomesforpatientswithCHBInconclusion,chronichepatitisB(CHB)remainsamajorhealthproblemworldwide,withhighratesofmorbidityandmortality.Treatmentoptionshaveimprovedinrecent