Gaia Silvia, Barbon Valeria, Smedile Antonina, Olivero Antonella, Carenzi Silvia, Lagget Marco, Alessandria Carlo, Rizzetto Mario, Marzano Alfredo
Department of Gastroenterology and Hepatology, ASO San Giovanni Battista, C.so Bramante 88, 10126 Turin, Italy.
J Hepatol. 2008 Apr;48(4):540-7. doi: 10.1016/j.jhep.2007.12.018. Epub 2008 Jan 31.
BACKGROUND/AIMS: In lamivudine-resistant patients with chronic hepatitis B (CHB), we compared efficacy, predictive response factors and changes in viral mutants in two antiviral approaches with adefovir.
A prospective cohort study on therapy with adefovir alone (29 patients) or combined with ongoing lamivudine (23 patients) was performed.
A virological response was achieved in 55% of patients treated with adefovir and in 83% of those treated with the combination (p>0.05). This response was directly related to the basal viral load (p<0.0001) and obtained in 10 patients with basal HBV-DNA<17,200 IU/ml using both strategies. In patients with a higher basal viral load, the virological response was more frequent when treated with the combination (p<0.05). Mutation at locus rt181 predicted HBV-DNA persistence during therapy. A virological rebound was observed in 18% of non-responders while on adefovir monotherapy.
To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine-resistant patients, rescue therapy is preferable at early evidence of genotypic resistance. However, in subjects with a significant viral load, combination therapy is more effective. The presence of the rt181 mutation is associated with incomplete response.
背景/目的：在对拉米夫定耐药的慢性乙型肝炎（CHB）患者中，我们比较了两种使用阿德福韦的抗病毒方法的疗效、预测反应因素及病毒突变体的变化。
进行了一项前瞻性队列研究，其中单独使用阿德福韦治疗的患者有29例，联合使用拉米夫定治疗的患者有23例。
接受阿德福韦治疗的患者中有55%实现了病毒学应答，联合治疗的患者中有83%实现了病毒学应答（p>0.05）。这种应答与基础病毒载量直接相关（p<0.0001），两种治疗策略在10例基础HBV-DNA<17,200 IU/ml的患者中均获得了病毒学应答。在基础病毒载量较高的患者中，联合治疗时病毒学应答更为常见（p<0.05）。rt181位点的突变可预测治疗期间HBV-DNA的持续存在。在接受阿德福韦单药治疗的无应答者中，有18%观察到病毒学反弹。
为在拉米夫定耐药患者中实现完全病毒学应答并降低阿德福韦耐药突变体的风险，在出现基因型耐药的早期证据时进行挽救治疗更为可取。然而，对于病毒载量较高的患者，联合治疗更有效。rt181突变的存在与不完全应答相关。
