恩替卡韦联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎患者的疗效观察

目的观察恩替卡韦联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎(CHB)患者的疗效和安全性。方法选取昆山市人民医院2011年5月至2013年5月门诊和住院的拉米夫定耐药患者45例,随机分成两组,治疗组23例应用恩替卡韦联合阿德福韦酯挽救治疗,对照组22例应用拉米夫定联合阿德福韦酯挽救治疗,观察两组治疗前及治疗后4、12、24、48周HBV DNA、ALT、AST、TBil、Alb、HBV血清学标志物含量变化以及治疗48周时非rtM204I位点变异发生率。计量资料组间比较用t检验,计数资料的组间比较用四格表χ2检验。结果治疗组挽救治疗后4、12周ALT、AST下降较对照组相比差异有统计学意义(t值为3.124、5.271、4.476、5.125,P值均0.01),挽救治疗24、48周后较对照组相比差异有统计学意义(t值为2.240、2.307、2.886、2.908,P值均0.05)。治疗4、12、24、48周后,治疗组HBV DNA转阴率分别为73.9%、86.8%、95.7%、100%,较对照组差异有统计学意义(χ2值为11.79、5.75、10.29、5.89,P值均0.05)。HBeAg阳性患者阴转率在治疗组及对照组间差异无统计学意义。治疗组48周后未出现新的非rtM204I位点变异,而对照组非rtM204I位点变异情况为4例,两组相比差异有统计学意义(χ2=4.59,P0.05)。结论恩替卡韦联合阿德福韦酯用于既往拉米夫定耐药的CHB患者的挽救治疗疗效明显,值得临床推广。

Clinical efficacy of combined treatment with entecavir and adefovir dipivoxil for lamivudine -resistant chronic hepatitis B

Objective To evaluate the efficacy and safety of the combined therapy with entecavir （ETV）and adefovir dipivoxil （ADV）in patients with lamivudine （LAM）-resistant chronic hepatitis B （CHB）.Methods A total of 45 patients who were diagnosed with LAM-resistant CHB and admitted to the Kunshan People＇s Hospital from May 2011 to May 2013 were recruited in this study and randomly divided to two groups.The treatment group included 23 CHB patients who received the combined therapy with ETV and ADV.The control group in-cluded 22 CHB patients who received the combined therapy with LAMand ADV.The changes in levels of HBV DNA,alanine aminotrans-ferase （ALT）,aspartate aminotransferase （AST）,total bilirubin （TBil）,albumin （Alb）,and HBV serum markers before and after 4,12, 24,and 48 weeks of treatment,as well as the rate of mutations other than that at rtM204I after 48 weeks of treatment,were measured in both groups.Comparison of continuous data between groups was made by t test,and comparison of categorical data by fourfold table chi -square test.Results The levels of ALT and AST in the treatment group were significantly lower than those in the control group after 4 and 12 weeks of treatment （t =3.124,5.271,4.476,5.125,all P 〈0.01 ）,as well as 24 and 48 weeks of treatment （t =2.240,2.307,2.886, 2.908,all P 〈0.05 ）.The serum HBV DNA clearance rates in the treatment group after 4,12,24,and 48 weeks of treatment were 73.9%,86.8%,95.7%,and 100%,respectively,all of which were significantly higher than those in the control group （χ2 =11.79, 5.75,10.29,5.89,respectively,all P 〈0.05）.However,there was no significant difference in the HBeAg seroconversion rate among HBeAg -positive patients between the two groups.No mutations other than that at rtM204I were found in the treatment group,while four new mutations were detected in the control group （χ^2 =4.59,P 〈0.05）.Conclusion The combined therapy with ETV and ADV has good therapeutic effect in treating LAM-resistant CHB patients,