CAJ | 학술논문

目的：对应用拉米夫定或阿德福韦酯治疗后耐药的慢性乙型肝炎患者给予联合治疗，观察治疗前后乙型肝炎病毒（HBV）变异模式的变化及对疗效的影响。方法在142例对拉米夫定耐药患者中，给予72例拉米夫定联合阿德福韦酯、70例给予恩替卡韦联合阿德福韦酯冶疗，在72例对阿德福韦酯耐药患者中，给予36例联合拉米夫定、另36例联合恩替卡韦治疗，各组均治疗48 w，测定和比较治疗前后所有患者 HBV DNA 聚合酶逆转录区相关变异位点变化。结果在拉米夫定初治发生耐药的患者中，发生 M204V 和 IL180M 变异率分别为98.6%（140/142）和56.3%（80/142），接受拉米夫定联合阿德福韦酯治疗患者 HBV DNA 阴转率为86.1%，与恩替卡韦联合阿德福韦酯治疗患者（97.1%）比，无显著性差异；在阿德福韦酯初治发生耐药的患者中，A181V 和 N236T 变异频率分别为63.9%（46/72）和52.8%（38/72），接受阿德福韦酯联合拉米夫定治疗患者 HBV DNA 阴转率为52.8%，显著低于阿德福韦酯联合恩替卡韦组（77.8%，P<0.05）；在阿德福韦酯联合拉米夫定治疗的36例患者中，19例（52.8%） HBV DNA 阴转，在阿德福韦酯联合恩替卡韦治疗的36例患者中，28例（77.8%）患者 HBV DNA 阴转，差异具有显著性（x2＝4.963，P<0.05）。结论以 rtM204变异为主的拉米夫定耐药在联合阿德福韦酯进行挽救治疗后疗效确定；以 rtA181变异为主的阿德福韦酯耐药患者在接受阿德福韦酯联合恩替卡韦治疗后的疗效优于联合拉米夫定。
목적：대응용랍미부정혹아덕복위지치료후내약적만성을형간염환자급여연합치료，관찰치료전후을형간염병독（HBV）변이모식적변화급대료효적영향。방법재142례대랍미부정내약환자중，급여72례랍미부정연합아덕복위지、70례급여은체잡위연합아덕복위지야료，재72례대아덕복위지내약환자중，급여36례연합랍미부정、령36례연합은체잡위치료，각조균치료48 w，측정화비교치료전후소유환자 HBV DNA 취합매역전록구상관변이위점변화。결과재랍미부정초치발생내약적환자중，발생 M204V 화 IL180M 변이솔분별위98.6%（140/142）화56.3%（80/142），접수랍미부정연합아덕복위지치료환자 HBV DNA 음전솔위86.1%，여은체잡위연합아덕복위지치료환자（97.1%）비，무현저성차이；재아덕복위지초치발생내약적환자중，A181V 화 N236T 변이빈솔분별위63.9%（46/72）화52.8%（38/72），접수아덕복위지연합랍미부정치료환자 HBV DNA 음전솔위52.8%，현저저우아덕복위지연합은체잡위조（77.8%，P<0.05）；재아덕복위지연합랍미부정치료적36례환자중，19례（52.8%） HBV DNA 음전，재아덕복위지연합은체잡위치료적36례환자중，28례（77.8%）환자 HBV DNA 음전，차이구유현저성（x2＝4.963，P<0.05）。결론이 rtM204변이위주적랍미부정내약재연합아덕복위지진행만구치료후료효학정；이 rtA181변이위주적아덕복위지내약환자재접수아덕복위지연합은체잡위치료후적료효우우연합랍미부정。
Objective To evaluate hepatitis B virus(HBV)mutations and its impact on antiviral effects in chronic hepatitis B(CHB)patients with mutants resistant to lamivudine or adefovir. Methods 142 nucleos(t)ide-naive CHB patients treated with lamivudine were switched to lamivudine plus adefovir (n=72) or entecavir plus adefovir (n=70) because of lamivudine resistance and 72 nucleos(t)ide-naive CHB patients treated with adefovir were switched to adefovir plus lamivudine (n=36) or adefovir plus entecavir (n=36) after resistance occurred. HBV DNA polymerase reverse transcriptase mutations were analyzed before and after 48 weeks of rescue therapy. Results Among CHB patients with lamivudine resistance,mutation patterns were mainly M204V and IL180M, with a frequency of 98.6%(140/142) and 56.3%(80/142),respectively;Undetectable serum HBV DNA were noted in 86.1% of patients in lamivudine and adefovir treatment group,and 97.1% of patients in entecavir and adefovir treatment group (P﹥0.05);Among CHB patients with adefovir resistance,A181V and N236T mutation rates were 63.9%(46/72) and 52.8%(38/72),respectively;Undetectable serum HBV DNA were found in 52.8%(19/36) of patients in adefovir and lamivudine treatment group,significantly lower than that [77.8% (28/36),x2=4.963,P﹤0.05] of patients in adefovir and entecavir treatment group. Conclusions Addition of adefovir dipivoxil to lamivudine is effective rescue therapy in patients with rtM204 mutation resistance to lamivudine,but in patients with rtA181 mutation resistance to adefovir dipivoxil,the addition of entecavir is superior to lamivudine.