CAJ | 학술논문

目的了解浙江省东部地区慢性乙型肝炎病毒(HBV)感染者阿德福韦酯(ADV)相关位点病毒变异的临床特征,为指导规范抗病毒治疗提供参考价值.方法回顾性分析宁波市第二医院2008年6月至2010年8月发生ADV相关位点病毒变异的慢性HBV感染者88例,并与同期未发生变异的202例患者进行对照,采用基因测序的方法对患者的血清标本进行P区耐药基因测序,同时检测HBV基因型、HBV血清学标志物、HBV DNA及肝脏影像学检查.结果 88例出现病毒变异的患者中,发现ADV预存变异9例;变异位点多而复杂,其他位点的变异均伴随ADV相关耐药位点的变异;单个位点变异以rtA181T为主(46.59％),其次为rtV214A( 11.36％),2个位点以上变异者27例(30.68％);变异组男性、终末期肝病、合并非酒精性脂肪肝(NAFLD)、C基因型HBV的构成比及年龄均高于无变异组(P＜0.01,＜0.01,0.019,0.045,＜0.01),而e抗原阳性状态的构成比及HBVDNA水平均低于无变异组(P=0.002,0.02).结论在未经ADV治疗的慢性HBV感染者中可能存在ADV相关位点的HBV预存基因变异;ADV相关位点的病毒变异以rtA181T变异为主,其次为rtV214A,且常伴存其他位点的多位点变异;HBV感染史较长、e抗原阴性、C基因型HBV感染、病情持续进展、合并NAFLD以及男性患者易出现ADV相关位点的病毒变异;患者应该接受和执行规范的抗病毒治疗和优化治疗,以实现预防耐药,避免挽救治疗.
목적 료해절강성동부지구만성을형간염병독(HBV)감염자아덕복위지(ADV)상관위점병독변이적림상특정,위지도규범항병독치료제공삼고개치.방법 회고성분석저파시제이의원2008년6월지2010년8월발생ADV상관위점병독변이적만성HBV감염자88례,병여동기미발생변이적202례환자진행대조,채용기인측서적방법대환자적혈청표본진행P구내약기인측서,동시검측HBV기인형、HBV혈청학표지물、HBV DNA급간장영상학검사.결과 88례출현병독변이적환자중,발현ADV예존변이9례;변이위점다이복잡,기타위점적변이균반수ADV상관내약위점적변이;단개위점변이이rtA181T위주(46.59％),기차위rtV214A( 11.36％),2개위점이상변이자27례(30.68％);변이조남성、종말기간병、합병비주정성지방간(NAFLD)、C기인형HBV적구성비급년령균고우무변이조(P＜0.01,＜0.01,0.019,0.045,＜0.01),이e항원양성상태적구성비급HBVDNA수평균저우무변이조(P=0.002,0.02).결론 재미경ADV치료적만성HBV감염자중가능존재ADV상관위점적HBV예존기인변이;ADV상관위점적병독변이이rtA181T변이위주,기차위rtV214A,차상반존기타위점적다위점변이;HBV감염사교장、e항원음성、C기인형HBV감염、병정지속진전、합병NAFLD이급남성환자역출현ADV상관위점적병독변이;환자응해접수화집행규범적항병독치료화우화치료,이실현예방내약,피면만구치료.
Objective To explore the clinical characteristics of hepatic B virus (HBV) mutations related to adefovir dipivoxil (ADV) among patients with chronic HBV infection in eastern Zhejiang province and provide some reference values on normative usage of antiviral drugs.Methods The data of chronic HBV-infected patients with HBV mutations related to ADV ( n =88 ) and non-mutation ( n =202 ) from June 2008 to August 2010 were analyzed retrospectively.The gene resistance mutations of HBV P region were analyzed by gene sequencing.And the HBV genotypes,HBV serum markers,HBV DNA levels and liver imaging findings were also analyzed.Results There were 9 cases with pre-existing mutations in 88 patients.The mutated sites were multiple and complicated.And the mutated sites related to other antiviral drugs were all accompanied by ADV-related mutations.The single mutated site was mostly at rtA181T (46.59％ ) and at rtV214A ( 11.36％ ).There were 27 cases (30.68％ ) with ≥ two mutated sites.The constituent ratios of males,end-stage liver diseases,complicated nonalcoholic fatty liver disease (NAFLD) and HBV genotype C infection in the mutation group were higher than those in the non-mutation group ( P ＜0.01,＜0.01,0.019,0.045).The average ages in the mutation group were also higher than those in the non-mutation group ( P ＜0.001 ).But the constituent ratios of HBeAg positivity and the levels of HBV DNAwere lower ( P =0.002,0.02 ).Conclusion There may be some cases with pre-existing ADV-related mutations in ADV treatment-naive patients.The mutated sites occur at multiple loci,mostly at rtA181T and rtV214A.The male patients and those with a longer history of HBV infection,HBeAg negativity,HBV genotype C infection,illness progression and complicated NAFLD may be more susceptible to mutation.It is important for patients to accept and implement standardized regimens of antiviral drugs so as to prevent resistance and avoid salvage therapy.