慢性乙型肝炎经治患者核苷类药物再治疗的效果与耐药分析  

Efficacy and drug resistance profiles of nucleosides retreatment in nucleoside experienced chronic hepatitis B patients

作　　者：谢榕[1] 江建宁[1] 苏明华[1] 刘志红[1] 钟少华[1] 何丽霞[1] 梁延秀[1] 黄小红[1] 郭稳稳[1] 符武岛[1] 胡家光[1] 祝美琴[1] 

机构地区：[1]广西医科大学第一附属医院感染性疾病科,南宁530021

出　　处：《中华传染病杂志》2012年第8期478-483,共6页Chinese Journal of Infectious Diseases

基　　金：广西自然科学基金资助项目（2010GXNSFD013046,桂科青0832037）;广西医学科学实验中心开放基金资助项目（KFJJ2010-20）;“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十二五”课题资助项目（2012ZX10002007）

摘　　要：目的探讨慢性乙型肝炎（cHB）经治患者核苷类药物（NA）再治疗的效果及其耐药情况。方法104例研究对象为初次无间断NA单药治疗至少3个月、停药后再次NA治疗至少1年的CHB患者。分为3组：A组39例，停药时已达慢性乙型肝炎防治指南中的停药标准；B组33例，停药时未达到停药标准但HBVDNA〈1．0×10^3拷贝／mL；C组32例，停药时未达到停药标准且HBVDNA〉1．0×10^3拷贝／mL。比较基线ALT、HBVDNA、HBeAg水平对再治疗的影响，以及3组患者不同再治疗方案的累计耐药率。套式PCR检测HBVP基因区耐药变异位点。统计学处理采用Wilcoxon秩和检验与y。检验。结果基线ALT〈1．3×正常值上限（ULN）的患者ALT复常时间为2个月，ALT≥1，3×ULN的患者ALT复常时间为4个月，差异有统计学意义（Z=2．281，P=0．023）；基线HBVDNA〈5lg拷贝／mL的患者病毒学应答时间为1个月，HBVDNA≥5lg拷贝／mL的患者为2个月，差异有统计学意义（z=2．054，P=0．040）；基线HBeAg阴性者病毒学应答及ALT复常时间分别为1个月和3个月，均早于HBeAg阳性者的2个月和4．5个月（z=2．580、2．304，均P〈0．05）。A组患者再治疗时病毒学应答时间及HBeAg血清学转换时间均比初次治疗快，分别为（1．61±1．76）、（3.38±3．34）个月和（3．48±4．06）、（9．92±11，22）个月（Z=2、854、-1．094，均P〈0．05）。A组病毒学应答时间早于B、C组，分别为（1。61±1．76）、（3．13±3．06）和（3．41±3．26）个月（z=-2．025，P〈0．01；z=-2．474，P〈0．05）。A组累计HBeAg血清学转换率高于B、C组，分别为80．0％、36．8％和37．5％（χ2=4．368、5．100，均P〈0．05）。共有13例发生耐药，4例检测到基因型耐药；继续原方案治疗C组累计耐药率明显高于A、B组，分别为44Yoo、9％和0（χ2=5．019、6．588，均P〈0．05）；采用无交叉耐药位点NA联合治疗�Objective To evaluate the efficacy and drug resistance profiles of nucleosides （NA） retreatment in NA experienced chronic hepatitis B （CHB） patients. Methods Totally 104 NA experienced CHB subjects were enrolled in this study. All these subjects had received at least 3 months NA monotherapy and stopped the treatment, and then received NA retreatment for at least one year. The subjects were divided into three groups according to the following criteria： reached the therapy endpoint of China guideline when they stopped NA-na[ve treatment （group A, n= 39）; did not reach the therapy endpoint when they stopped NA-na^ve treatment but hepatitis B virus （HBV） DNA（ 1.0X 103 copy/mL （group B, n=33） ; and with HBV DNA^I. 0X 103 copy/mL （group C, n=32）. The efficacy and drug resistance profiles of retreatment were compared among three groups. The effects of baseline alanine aminotransferase （ALT） levels, HBV DNA levels and HBeAg titers on the retreatment efficacies were analyzed. The mutations of HBV P gene were detected by nested polymerase chain reaction （PCR） and direct sequencing. The data were analyzd by Wilcoxon test and ）i2 test. Results The time to ALT normalization in patients with baseline ALT（1. 3 X upper limit normal （ULN） was shorter than that in patients with ALTO1.3 X ULN （2 months vs 4 months; Z= 2. 281, P=0. 023）. The time to Virological response in patients with baseline HBV DNA5 lg copy/ mL was shorter than that in patients with HBV DNA^5 lg copy/mL （1 month vs 2 months; Z= 2. 054, P = 0. 040）. The time to virological response and ALT normalization in baseline HBeAg negative were both shorter than those in patients with baseline HBeAg positive patents （1 month vs 3 months and 2 months vs 4. 5 months, respectively; Z= 2. 580 and 2. 304, respectively; both P〈0.05）. The subjects in group A achieved virological response and HBeAg seroconversion after retreatment earlier compared to previous NA-nave therapy （[1.61±1.76] months vs [3.48 ±4.06] months a

关 键 词：肝炎 乙型 慢性 核苷类 抗病毒药 抗药性 病毒 再治疗 变异(遗传学) 

分 类 号：R512.62[医药卫生—内科学]