Fung Scott K, Andreone Pietro, Han Steve H, Rajender Reddy K, Regev Arie, Keeffe Emmet B, Hussain Munira, Cursaro Carmela, Richtmyer Pamela, Marrero Jorge A, Lok Anna S F
Division of Gastroenterology, University of Michigan, Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA.
J Hepatol. 2005 Dec;43(6):937-43. doi: 10.1016/j.jhep.2005.05.037. Epub 2005 Jul 7.
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.
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.
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 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 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 > or = 3 log10 was seen in 3 patients.
In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.
背景/目的：在体外研究中，对阿德福韦耐药的乙型肝炎病毒（HBV）突变体的敏感性仅降低3至10倍，这表明病毒学突破和临床恶化不太可能发生。本研究的目的是描述阿德福韦耐药HBV感染患者的临床病程。
对接受阿德福韦治疗反应欠佳或出现病毒学突破的患者进行阿德福韦耐药突变检测。使用线性探针分析和HBV P基因直接测序检测阿德福韦耐药突变。
8例先前存在拉米夫定耐药或突破的男性患者（平均年龄47±13岁）被发现存在阿德福韦耐药突变rtA181V/T或rtN236T。基线时ALT中位数为66 IU/L（范围27 - 1161），HBV DNA中位数为7.9 log10拷贝/ml（范围6 - 8.3）。在出现阿德福韦耐药时（平均20±9个月），7例患者的HBV DNA增加至≥5 log10拷贝/ml。在检测到阿德福韦耐药后，2例患者发生肝失代偿，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挽救治疗，3例患者的HBV DNA降低≥3 log10。
总之，阿德福韦耐药可能与显著的病毒反弹和肝失代偿相关，这可能是致命的。
