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目的观察HBV逆转录酶区181位点T/V突变(HBV rtA181T/V)患者的抗病毒治疗史、血清学特点、恩替卡韦挽救治疗效果。方法连续入组71例已经出现病毒学突破的核苷(酸)类似物(NAs)耐药乙肝患者。均采用直接测序法行HBV测序,且证实存在HBV rtA181T/V,其中HBV rtA181T突变41例、HBV rtA181V突变30例。回顾71例患者的NAs用药史。检测并比较rtA181T、rtA181V患者出现病毒学突破时的血清ALT、HBsAg、HBV-DNA水平。所有患者采用恩替卡韦为主的挽救方案治疗,比较rtA181T、rtA181V患者治疗24、52周时的病毒学应答情况。结果 71例患者中既往应用单一NAs者为25例(以阿德福韦酯为主),序贯或联合应用多种NAs者46例。HBV rtA181T、rtA181V患者病毒学突破时中位血清ALT水平分别为55(15,474)、49(16,183)U/L,P>0.05;血清HBV-DNA的log10分别为5.71±1.02、6.04±0.97,P>0.05;血清HBsAg的log10分别为3.36±0.50、3.64±0.60,P<0.05。用以恩替卡韦为主的挽救方案治疗24周,病毒学完全应答55例(77.5%),病毒学不完全应答16例(22.5%),其中HBV rtA181T、rtA181V患者分别有33(80.5%)、22例(73.3%)达到病毒学完全应答,HBV rtA181T、rtA181V患者病毒学完全应答率相比P>0.05;治疗52周时病毒学完全应答62例(87.3%),病毒学不完全应答9例(12.7%),其中HBV rtA181T、rtA181V患者分别有37(90.2%)、25例(83.3%)达到病毒学完全应答,HBV rtA181T、rtA181V患者病毒学完全应答率相比P>0.05。结论 HBV rtA181T/V突变患者多为序贯或联合应用阿德福韦酯及拉米夫定等多种NAs。HBV rtA181V患者发生病毒学突破时血清HBsAg水平高于HBV rtA181T患者。HBV rtA181T/V突变患者应用恩替卡韦挽救治疗效果满意,但HBV rtA181T、rtA181V患者治疗效果比较无统计学差异。
Objective To observe the history of antiviral therapy, serological features and entecavir treatment in patients with HBV TERT mutation 181 (HBV rtA181T / V) in HBV reverse transcriptase region. Methods A total of 71 patients with virological breakthrough of nucleoside (acid) analogue (NAs) resistant hepatitis B virus were enrolled in this study. HBV sequencing was performed by direct sequencing, and HBV rtA181T / V was confirmed. Among them, 41 cases were HBV rtA181T mutation and 30 cases were HBV rtA181V mutation. The history of NAs in 71 patients was reviewed. Detection and comparison of rtA181T, rtA181V patients with virological breakthrough serum ALT, HBsAg, HBV-DNA levels. All patients were treated with entecavir-based salvage regimen. The virological responses at rtA181T and rtA181V were compared at 24 and 52 weeks. Results Among the 71 patients, there were 25 cases with predominantly single NAs (adefovir dipivoxil prednisone) and 46 cases with multiple NAs either sequential or combined. The median serum ALT levels of HBV rtA181T and rtA181V patients were 55 (15,474) and 49 (16,183) U / L, respectively, and the log10 of serum HBV-DNA were 5.71 ± 1.02,6.04 ± 0.97 > 0.05. The log10 of serum HBsAg were 3.36 ± 0.50 and 3.64 ± 0.60 respectively, P <0.05. There were 55 cases (77.5%) with complete virological response and 16 cases (22.5%) with incomplete virological response. The patients with HBV rtA181T and rtA181V had 33 (80.5%), 22 (73.3%) achieved complete virological response, HBV rtA181T, rtA181V virological complete response rate compared to P> 0.05; 52 weeks of virological complete response in 62 cases (87.3%), virological incomplete response in 9 cases ( 12.7%). HBV rtA181T and rtA181V patients had 37 (90.2%) and 25 (83.3%) patients, respectively. Virologic complete response was achieved in HBV rtA181T and rtA181V patients. Conclusions Many patients with HBV rtA181T / V mutation often have multiple NAs such as adefovir dipivoxil and lamivudine. HBV rtA181V patients with virological breakthrough when the serum HBsAg levels higher than HBV rtA181T patients. In patients with HBV rtA181T / V mutation, the effect of entecavir was satisfactory, but there was no significant difference in the therapeutic effect between rtA181T and rtA181V patients.