De Francesco Maria Antonia, Gargiulo Franco, Spinetti Angiola, Zaltron Serena, Giagulli Cinzia, Caccuri Francesca, Castelli Francesco, Caruso Arnaldo
Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, Italy.
New Microbiol. 2015 Jan;38(1):29-37. Epub 2015 Jan 1.
Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.
对于出现耐药的慢性乙型肝炎（CHB）患者的最佳管理方法，人们知之甚少。本研究的目的是调查不同药物方案对慢性HBV感染患者的有效性。使用分支DNA分析法测定HBV病毒载量，并通过聚合酶测序试验研究HBV-DNA中的替代情况。该研究纳入了38例拉米夫定（LAM）治疗失败的患者。依次使用的治疗方法为：LAM+阿德福韦（ADV）、LAM+替诺福韦（TDF）、恩替卡韦（ETV）单药治疗、ADV单药治疗和TDF单药治疗。所有药物方案均观察到对HBV复制有相似的活性。在接受LAM治疗的患者中，44%出现了耐药突变。rt M204I突变更为常见。依次加用ADV的LAM和TDF治疗分别在3/18（16.6%）和1/8（5.5%）的治疗患者中诱导出现耐药。D基因型最为常见（78.9%），其次是A基因型（13%）、E基因型（5.2%）和C基因型（2.6%）。我们的研究表明，基线血清HBV DNA是病毒学应答的重要预测指标，且病毒学突破与基因型耐药的出现显著相关。
