S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse 英文参考文献.docVIP

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S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse 英文参考文献.doc

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S-Adenosyl-MethionineandBetaineImproveEarly VirologicalResponseinChronicHepatitisCPatientswith PreviousNonresponse MagdalenaFilipowicz1,2,ChristineBernsmeier1,2,LuigiTerracciano3,FrancoisH.T.Duong1,MarkusH. Heim1,2 * 1Hepatology Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland, 2Department of Gastroenterology and Hepatology, University HospitalBasel,Basel,Switzerland,3InstituteforPathology,UniversityHospitalBasel,Basel,Switzerland Abstract Background/Aims:TreatmentofchronichepatitisC(CHC)withpegylatedinterferona(pegIFNa)andribavirinresultsina sustainedresponseinapproximatelyhalfofpatients.ViralinterferencewithIFNasignaltransductionthroughtheJak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiateIFNasignalinginculturedcellsthatexpresshepatitisCvirus(HCV)proteins,andenhancetheinhibitoryeffectof IFNaonHCVreplicons.Wehaveperformedaclinicalstudywiththeaimtoevaluateefficacyandsafetyoftheadditionof SAMeandbetainetotreatmentofCHCwithpegIFNa/ribavirin. Methods:Inthisopen-labelpilotstudy,29patientswithCHCwhofailedprevioustherapywith(peg)IFNa/ribavirinwere treatedwithSAMe,betaine,pegIFNa2bandribavirin.Treatmentdurationwas6or12months,dependingongenotype,and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemicalresponseandsafetywereassessedthroughoutthetreatment. Results: 29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype1,72%hadadvancedfibrosis,76%hadpreviouslyreceivedpegIFNa/ribavirin,andonly14%achievedEVRtothe previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achievedasustainedvirologicalresponse(SVR).SAMeandbetainewerefoundtobesafewhenusedwithpegIFNa/ribavirin. Conclusion:TheadditionofSAMeandbetainetopegIFNa/ribavirinimprovesearlyvirologicalresponseinCHC. Tri