慢性乙型肝炎抗病毒治疗进展

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2009369··CHINAMEDICALHERALD1,2*(1.,028000;2.○,100039)[]、(α-2aα-2b)、、、、、、。[];;;HBV[]R512.6+2[]B[]1673-7210(2009)03(c)-009-03*20HBV,3~4HBV,25%~40%。,3851HBsAg13,HBVDNA,(HCC)。,、、。,、(α-2aα-2b)、、、、。、,,。1()1.1HBV,(HCC)。,。,(CHB),,。,,。1.2,500U,1;(α-2aα-2b),180(80)μg,,1;1。1.3,①:、、、、、、、、;②:、、、、;③:、、、、、;④:、、;⑤:,、;⑥:、、、、、;⑦:、;⑧:、、。、,,、,。2(lamivudine,LAM)LAM,1998、,HBV,、,。2.1LAM。Liaw、、651(Child-Pugh≥4),2∶1LAM()。3,LAM()(Child-Pugh≥2、、、)9%21%(P=0.001)HCC5%10%(P=0.023)。LAM,LAM。HBsAg,,HBVDNAALT,。LAM,,HBsAgHBV,,LAM,,LAM。2.2100mg/d,。:①,,HBeAg,;②,,,、;③,HBVYMDD(resistantmutation),HBVDNAALT,。LAM:Lai,1、2、3、4、5,24%、42%、53%、67%、69%。,、,,,,LAM,,,LAM,,LAM。3(adefovir,ADV)3.13.1.1HBeAg(+)HBeAg(-)Marcellin、Hadziyannis、,ADV10mg/d309HBeAg(+)92009369··CHINAMEDICALHERALD144,HBeAg(-)185240。HBeAg(+)48、96144,HBVDNA(1000cps/ml)28%、45%56%;HBeAg21%、42%51%;HBeAg12%、29%43%;ALT58%、71%、81%;489659%53%;79%71%;54%41%。HBeAg(-)48、96、144、192240,HBVDNA(1000cps/ml)68%、71%、77%、78%67%;ALT75%、72%、67%、75%69%;489664%79%。ADVHBeAg(+)HBeAg(-),HBVDNA、ALT,。3.1.2LAM,ADVLAM,LAMYMDD,HBVDNA。LAM,ADV+LAMADV,ADVADV。3.1.3、LAMOsborn12244LAM,30,ADV,LAM。,ADV,,、,HBVLAM。3.2ADV,、。ADV,ADV10mg/d48,960.5mg/dl2.5%,1444.2%。,ADV,。,ADV48,HBVP。96、144、192、240,HBVDNADN236TBA181V,3%、11%、18%29%。,ADV,ADV,HBVDNAALT,。N236T,LAM,ADVLAM,。,ADV(ETV)。4(entecavir,ETV)ETV,。HBV,HBVLAM300。:0.5mg/d;LAMl.0mg/d。4.14.1.1,HBeAg(+)HBeAg(-)CHB,ETV2,HBVDNA、HBVDNA、ALTLAM。4.1.2LAMLAM,ETV1(1mg/d)、241%HBVDNA,3,3HBV,ETV。4.2ETVLAM。,YMDDT184G、S202I、M250V,ETV。,ETVLAM,ETVLAM,ETV。5(Telbivudine,LdT)、、LdTLAM2,201367CHB,LdT600mg/dpo100mg/dpo2,,HBeAg(+)HBeAg(-),LdTHBVDNAlog10、PCR、HBeAgLAM。LdT,YMDD,,LAM。LdTLAM,,,、。6(TDF)、(FTC)(CLV)。TDF,LAM。FTCCLVHBVDNA、ALT。FTCLAM,48,YMDD12.6%;CLV。7,5,,,,;,,,;,,,,。,HBV,,,,。HBV,,,。HBV,,,;,;,HBV。、,。,HBV,HBV,、,(),,,,、、,,,。102009369··CHINAMEDICALHERALD[][1]BaumertTF,ThimmeR,vonWeizsackerF.PathogenesisofhepatitisBvirusinfection[J].WorldJGastroenterol,2007,13(1):82-90.[2]LiawYF,SollanoJD.FactorsinfluencingliverdiseaseprogressioninchronichepatitisB[J].LiverInt,2006,26(Suppl2):23-29.[3]YaoX,ZhengB,ZhouJ,etal.TherapeuticeffectofhepatitisBsurfaceantigen-antibodycomplexisassociatedwithcytolyticandnon-cytolyticimmuneresponsesinhepatitisBpatients[J].Vaccine,2007,25(10):1771-1779.[4]ChangJJ,LewinSR.ImmunopathogenesisofhepatitisBvirusinfection[J].ImmunolCellBiol,2007,85(1):16-23.[5]LAICL.TherapeuticadvancesinchronichepatitisB[J].JGastroenterolHepatol,2004,19(Suppl):S5-9.[6]ChanHLY,WongVWS,TseAML,etal.SerumHepatitisBSurfaceAntigenQuantitationCanReflectHepatitisBVirusintheLiverandPredictTreatmentResponse[J].ClinGastroenterolHepatol,2007,5(12):1462-1468.[7]PerrilloR,HannH-W,MutimerD,etal.AdefovirdipivoxiladdedtoongoinglamivudineinchronichepatitisBwithYMDDmutanthepatitisBvirus[J].Gastroenterology,2004,126(1):81-90.[8]KuwaharaR,KumashiroR,InoueA,etal.Adefovirdipivoxilasatreat-mentforhepaticfailurecausedbylamivudine-resistantHBVstrains[J].DigDisSci,2004,49(2):300-303.[9]ChangTT,GishRG,deManR,etal.AcomparisonofentecavirandlamivudineforHBeAg-positivechronichepatitisB[J].NEnglJMed,2006,354(10):1001-1010.[10]LaiCL,ShouvalD,LokAS,etal.Entecavirversuslamivudineforpa-tientswithHBeAg-negativechronichepatitisB[J].NEnglJMed,2006,354(10):1011-1020.[11]TenneyDJ,LevineSM,RoseRE,etal.Clinicalemergenceofente-cavir-resistanthepatitisBvirusrequiresadditionalsubstitutionsinvirusalreadyresistanttoLamivudine[J].AntimicrobAgentsChemother,2004,48(9):3498-3507.[12],,,.[J].,2005,10(1):2-4.[13]AnnaS.Lok,FabienZoulim,StephenLocarnini,etal.AntiviralDrug-ResistantHBV:StandardizationofNomenclatureandAssaysandRec-ommendationsforManagement[J].Hepatology,2007,46(1):254-265.[14]Bartholomeusz,Locarnini.Antiviraldrugresistance[J].SeminarsinLiverDisease,2006;26(2):161-170.[15]YimHJ,HussainM,LiuY,etal.EvolutionofMulti-DrugResistantHepatitisBVirus[J].DuringSequentialTherapy.Hepatology,2006,44(3):703-712.(:2008-09-22)(,300102)[](DR)。,、DR、。C(PKC),,,、、(DME)、。[];;[]R774[]A[]1673-7210(2009)03(c)-011-02(diabeticretinopathy,DR),。DR,,,DR,DR[1]。,,DR。DR、、,:,、,-、、,,,。,,、、。1DR、,、DR。,≥11.1mmol/LDR≤7.8mmol/L3.6。7.90mmol/LDR,7.15mmol/LDR。,、、,[2]。2DR、,。UKPDS(UnitedKingdomprospectivediabetesstudy)1148,,(DME)DR。(AEC),,AEC--,,,,。,[3]。11

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