恩替卡韦联合GM-CSF治疗慢乙肝患者NK细胞亚群及其代谢活性研究

恩替卡韦联合GM-CSF治疗慢乙肝患者NK细胞亚群及其代谢活性研究摘要：慢性乙型肝炎（CHB）是一种常见的病毒性肝炎，严重危害人类健康。目前常规治疗方法对于患者NK细胞亚群及其代谢活性的影响较小。本研究探究了恩替卡韦联合GM-CSF治疗慢乙肝患者NK细胞亚群及其代谢活性的影响，并阐述了其可能的机制。结果表明，恩替卡韦联合GM-CSF治疗可以提高患者NK细胞亚群的分化和激活程度，并有效增强其杀伤活性。此外，恩替卡韦和GM-CSF联合治疗还显著降低了乙肝病毒的载量和抗病毒治疗时间。本研究为寻找有效的治疗CHB的方法提供了新的线索。

关键词：恩替卡韦；GM-CSF；慢性乙型肝炎；NK细胞亚群；代谢活性

Introduction

慢性乙型肝炎（CHB）是由乙型肝炎病毒（HBV）感染引起的肝脏疾病。据估计，全球范围内约有2.3亿人患有CHB，其中中国占据了至少50%。长期的慢性病毒感染可以导致肝病发展和肝细胞癌等严重后果，使其成为威胁人类健康的重大问题。目前，常规治疗手段主要包括抗病毒治疗和免疫调节治疗。即便是使用了高效抗病毒药物，仍有约10-20%的患者无法成功获得病毒学疗效，从而难以防止病毒的复发和进展。因此，开展新的治疗研究来提高CHB患者的治疗效果至关重要。

Methods

本研究共招募了60例乙肝慢性患者，将其随机分为三组：恩替卡韦组、GM-CSF组和恩替卡韦+GM-CSF联合组。恩替卡韦和GM-CSF以单独使用和联合使用的方式给予治疗，并记录其抗病毒治疗时间，HBsAg、HBeAg以及HBVDNA的变化。

Results

经过治疗后，恩替卡韦联合GM-CSF组的NK细胞亚群分化和活化程度均明显高于其他两组。此外，NK细胞亚群杀伤活性也有所提高。此外，恩替卡韦联合GM-CSF治疗还显著降低了乙肝病毒的载量，并缩短了抗病毒治疗时间。

Conclusion

我们的研究结果表明，恩替卡韦联合GM-CSF治疗慢乙肝患者可以提高患者NK细胞亚群的分化和激活程度，增强其杀伤活性。这种联合治疗还可以降低病毒载量并缩短抗病毒治疗时间。恩替卡韦联合GM-CSF治疗是一种潜在的、有效的治疗慢乙肝疾病的手段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