摘要
目的评价恩替卡韦对阿德福韦酯耐药患者的疗效及肾脏安全性,同时对比分析恩替卡韦对阿德福韦酯不同耐药位点的疗效,为临床抗乙型肝炎病毒(HBV)治疗药物选择提供依据。方法选取阿德福韦酯耐药的慢性乙型肝炎患者60例,给予恩替卡韦治疗。比较恩替卡韦对阿德福韦酯耐药患者不同时间(基线、12、24、36、48周)的疗效[谷丙转氨酶(ALT)复常率、乙型肝炎病毒核糖核酸(HBV-DNA)阴转率、乙肝表面抗原(HBsAg)]、肾功能[血肌酐(Scr)及肾小球滤过率(eGFR)水平]及不同耐药位点[控制区D区236位点的天冬酰胺被苏氨酸替代(rtN236T)及控制区B区181位点的丙氨酸被缬氨酸/苏氨酸替代(rtA181V/T)]的疗效(ALT复常率、HBV-DNA阴转率、HBsAg水平)。结果60例患者基线、12、24、36、48周的ALT复常率分别为20.0%、38.3%、61.7%、80.0%及93.3%,基线、12、24、36、48周的HBV-DNA阴转率分别为0、25.0%、63.3%、70.0%和85.0%;患者的ALT复常率和HBV-DNA阴转率均随着治疗时间的延长而升高,差异具有统计学意义(P<0.05)。患者在12、24、36、48周的HBsAg滴度与基线比较差异无统计学意义(P>0.05)。5例患者出现SCr轻度升高且eGFR<90 ml/L,随着治疗时间的延长,SCr和eGFR逐渐恢复,治疗48周时SCr和eGFR均恢复正常,其余患者无SCr升高及eGFR下降。60例阿德福韦酯耐药患者中rtA181V/T位点28例,rtN236T位点32例,耐药多发生在15~34个月,平均18个月。恩替卡韦对阿德福韦酯rtN236T和rtA181V/T耐药位点在12、24、36、48周的ALT复常率、HBV-DNA阴转率及HBsAg比较差异无统计学意义(P>0.05)。结论阿德福韦酯长期应用可出现耐药,rtA181V/T和rtN236T出现几率相近,恩替卡韦对于阿德福韦酯耐药的挽救治疗的疗效及安全性良好,恩替卡韦对于阿德福韦酯不同耐药位点疗效相同。
Objective To evaluate the clinical efficacy and safety of entecavir in chronic hepatitis B patients with resistance to adefovir dipivoxil,comparatively analyze the efficacy of entecavir on different drugresistant sites of adefovir dipivoxil,so as to provide basis for clinical selection of medication for anti-hepatitis B virus(HBV).Methods 60 chronic hepatitis B patients with resistance to adefovir dipivoxil were selected and treated with entecavir.The efficacy[alanine aminotransferase(ALT)normalization rate,hepatitis B virus deoxyribonucleic acid(HBV-DNA)negative-conversion rate,hepatitis B surface antigen(HBsAg)]and renal function[serum creatinine(Scr)and estimated glomerular filtration rate(eGFR)]of entecavir on patients with adefovir dipivoxil resistance at different time[baseline,12 weeks,24 weeks,36 weeks,48 weeks],and efficacy[ALT normalization rate,HBV-DNA negative-conversion rate,HBsAg]at different resistance sites[asparagine at position 236 in the control area D was replaced by threonine(rtN236T)and the alanine at position 181 in the control area B was replaced by valine/threonine(rtA181V/T)].Results At baseline,12 weeks,24 weeks,36 weeks and 48 weeks,the normalization rate of 60 patients were 20.0%,38.3%,61.7%,80.0%and 93.3%,and HBV-DNA negative-conversion rate were 0,25.0%,63.3%,70.0%and 85.0%.The ALT normalization rate and HBV-DNA negative-conversion rate increased with the extension of treatment time,and the difference was statistically significant(P<0.05).There was no statistically significant difference in HBsAg titer at 12,24,36 and 48 weeks from baseline(P>0.05).5 patients had a slight increase in SCr and eGFR<90 ml/L.With the extension of the treatment time,SCr and eGFR gradually recovered.After 48 weeks of treatment,both SCr and eGFR returned to normal.The remaining patients had no increase in SCr and decrease in eGFR.Among the 60 patients with resistance to adefovir dipivoxil,28 cases were at rtA181V/T site and 32 cases were at rtN236T site.The drug resistance mostly occurred in 15-34 months,with an average of 18 months.There was no statistically significant difference in ALT normalization rate,HBV-DNA negative-conversion rate and HBsAg at 12,24,36,and 48 weeks of entecavir to adefovir dipivoxil at rtN236T and rtA181V/T resistance sites(P>0.05).Conclusion Long-term application of adefovir dipivoxil may cause drug resistance,and the occurrence rates of rtA181V/T and rtN236T are similar.Entecavir has good efficacy and safety in the rescue treatment of adefovir dipivoxil resistance,and entecavir has the same effect on different resistance sites of adefovir dipivoxil.
作者
邢文斌
安雪婷
郭晓楠
侯金玲
XING Wen-bin;AN Xue-ting;GUO Xiao-nan(Department of Liver Diseases,Dalian Sixth People’s Hospital,Dalian 116031,China)
出处
《中国实用医药》
2021年第14期111-114,共4页
China Practical Medicine
基金
大连市医学科学研究计划项目资助(项目编号:171105)。