Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation
Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation
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DOI：
10.1016/j.jhep.2005.05.037
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发表时间：
2005-12-01
影响因子：
25.7
通讯作者：
Lok, ASF
中科院分区：
文献类型：
--
作者：
Fung, SK;Andreone, P;Lok, ASF
背景/目的：在体外研究中，对阿德福韦耐药的乙肝病毒突变株的易感性仅降低3-10倍，这表明病毒学上的突破和临床恶化是不可能的。本研究的目的是描述对阿德福韦耐药的乙肝病毒感染患者的临床病程。方法：对阿德福韦疗效不佳或病毒学突破的患者进行阿德福韦耐药突变检测。结果：8例既往存在拉米夫定耐药或突破的男性患者(平均年龄47+/-13岁)存在阿德福韦耐药突变rtA181V/T或rtN236T。基线ALT中位数为66IU/L(范围27~1161)，HBVDNA7.9log(10)拷贝/ml(范围6~8.3)。在阿德福韦耐药时(平均20+/-9个月)，7例患者HBVdna升高至5log(10)拷贝/ml。检测阿德福韦耐药后，2例患者出现肝功能失代偿，其中1例死亡。7例患者接受了拉米夫定、恩替卡韦或替诺福韦的抢救治疗，3例患者的HBVDNA下降，其下降幅度为-gt；=3log(10)。结论：阿德福韦耐药可导致明显的病毒反弹和肝功能失代偿，这可能是致命的。(C)2005年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection.Methods: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene.Results: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47 +/- 13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log(10) copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20 +/- 9 months), HBV DNA increased to >= 5 log(10) copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by >= 3 log(10) was seen in 3 patients.Conclusions: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.