CAJ | 학술논문

目的探讨拉米夫定长期治疗慢性乙型肝炎(CHB)患者的耐药因素及其耐药后处理措施,为合理应用拉米夫定提供依据.方法 2001年9月-2010年1月应用拉米夫定初治的CHB患者383例,治疗观察满1年.其中发生病毒学突破或反弹患者129例,分为换用阿德福韦酯治疗组和加用阿德福韦酯治疗组.疗效评估包括血清HBV病毒学、血清HBV免疫学、血生物化学应答,观察时间至少1年.定性资料采用X2检验,反弹时间分布关系用生存分析曲线描述.结果383例CHB患者3个月、半年、1、2、3年以及3年后HBV DNA阴转率分别为40.7%、55.6%、59.5%、56.7%、55.9%和55.6%.HBeAg血清学转换62例,占22.6%.原发耐药12例,突破反弹129例,累计耐药率为36.8%,累计反弹率为34.8%.基线高病毒载量、基线ALT水平<2倍正常值上限、治疗24周时的病毒学低应答,与较高的反弹率相关,X2值分别为35.716、8.728和43.534,P值均<0.01.病毒学突破反弹发生在1年半内112例(86.8%),2年内123例(95.3%),5年以后未再发现病毒学突破反弹患者.129例病毒学突破反弹的患者予以换用阿德福韦酯或加用阿德福韦酯继续治疗,换药和加药后的再次阴转率分别为22.7%(15/66)和58.7%(37/63),病毒学应答率分别为59.1%(39/66)和87.3%(55/63),x2值分别为17.364和12.975,P值均<0.01,差异有统计学意义.结论拉米夫定初始治疗的CHB患者,耐药反弹主要发生在2年以内,对于拉米夫定耐药的CHB患者,拉米夫定联合阿德福韦酯比单用阿德福韦酯治疗可取得更好的疗效.
목적 탐토랍미부정장기치료만성을형간염(CHB)환자적내약인소급기내약후처리조시,위합리응용랍미부정제공의거.방법 2001년9월-2010년1월응용랍미부정초치적CHB환자383례,치료관찰만1년.기중발생병독학돌파혹반탄환자129례,분위환용아덕복위지치료조화가용아덕복위지치료조.료효평고포괄혈청HBV병독학、혈청HBV면역학、혈생물화학응답,관찰시간지소1년.정성자료채용X2검험,반탄시간분포관계용생존분석곡선묘술.결과383례CHB환자3개월、반년、1、2、3년이급3년후HBV DNA음전솔분별위40.7%、55.6%、59.5%、56.7%、55.9%화55.6%.HBeAg혈청학전환62례,점22.6%.원발내약12례,돌파반탄129례,루계내약솔위36.8%,루계반탄솔위34.8%.기선고병독재량、기선ALT수평<2배정상치상한、치료24주시적병독학저응답,여교고적반탄솔상관,X2치분별위35.716、8.728화43.534,P치균<0.01.병독학돌파반탄발생재1년반내112례(86.8%),2년내123례(95.3%),5년이후미재발현병독학돌파반탄환자.129례병독학돌파반탄적환자여이환용아덕복위지혹가용아덕복위지계속치료,환약화가약후적재차음전솔분별위22.7%(15/66)화58.7%(37/63),병독학응답솔분별위59.1%(39/66)화87.3%(55/63),x2치분별위17.364화12.975,P치균<0.01,차이유통계학의의.결론랍미부정초시치료적CHB환자,내약반탄주요발생재2년이내,대우랍미부정내약적CHB환자,랍미부정연합아덕복위지비단용아덕복위지치료가취득경호적료효.
Objective To study the factors influencing the long-term usage of lamivudine(LAM)in chronic hepatitis B(CHB)patients and the management after drug-resistance.Methods 383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine (100mg/d)and followed up for at least over 1 year from 2001 to 2010.129 cases encountered lamivudine-resistance and were then divided into two groups:patients in group A were switched to adefovir dipivoxil(ADV)alternative treatment and those patients in group B were added with ADV for continuous treatment.Efficacy assessment factors included serum HBV markers,HBV DNA,ALT,AFP and other biochemical indicators.Results Among the 383 cases,patients with HBV DNA negative conversion(PCR below test line)at 3 months,6 months,1 year,2 years,3years and>3 years after initial treatment were respectively 156 cases(40.7%),213 cases(55.6%),228 cases (59.5%),217cases(56.7%),214 cases(55.9%)and 213 cases(55.6%).HBeAg/HBeAb seroconversion occurred in 62 cases(22.6%).12 cases were found with primary LAM resistance,129 cases with HBV breakthrough and rebound.the cumulative resistance rate was 36.8%and the cumulative rebomad rate was 34.8%.High baseline viral load,baseline ALT levels < 2 ULN,Lower virologic response rate at week 24 were associated with a higher rebound rate ( x2 is 35.716,8.728,43.534,respectively,all with P < 0.01).Viral breakthrough and rebound occurred in 112 patients (86.8%) within 1 year and a haf,123 patients (95.3%)occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B,the rates of HBV DNA loss were 22.7% (15/66)and 58.7% (37/63) respectively,and the viral response rates were 59.1% (39/66) and 87.3% (52/63)respectively,with x2 values equaled 17.364 and 12.975 respectively (P < 0.01). Conclusion For the chronic hepatitis B patients on initial treatment with lamivudine,the viral rebound occurred mainly within 2 years. LAM combined with ADV is more effective than ADV alone for lamivudine-resistant patients.