Division of Gene and Cell-based Therapy, Department of Liver Studies and Transplantation, King's College London, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK.
Expert Opin Investig Drugs. 2009 Nov;18(11):1655-66. doi: 10.1517/13543780903241599.
Nucleos(t)ide analogues, active against hepatitis B polymerase, suppress viral replication and improve clinical outcome. However, the emergence of drug-resistant mutants can result in treatment failure.
We describe how the choice of first-line therapy is critical to long-term treatment success.
A review of current drug therapies is provided.
RESULTS/CONCLUSIONS: Monotherapy with early-generation drugs (lamivudine or adefovir) was associated with a high rate of viral drug resistance and combination therapy with these agents was shown to reduce the incidence of resistance. The latest-generation drugs (entecavir and tenofovir) are potent inhibitors of viral replication and, in treatment-naive subjects, viral resistance to entecavir is uncommon and is not yet reported to tenofovir. Therefore, monotherapy with either entecavir or tenofovir is the current preferred option in treatment-naive patients. Combination therapy is appropriate in those with drug-resistant HBV infection, where drug choice is guided by the viral drug-resistance genotype/phenotype. Although combination therapy has been advocated in other patient groups (e.g., those with decompensated cirrhosis and following liver transplantation), there are, as yet, no data to mandate the use of combination therapy in such patients and any perceived benefit must be weighed against increased cost and risk for toxicity.
核苷（酸）类似物可有效抑制乙型肝炎聚合酶，从而抑制病毒复制，改善临床结局。然而，耐药突变体的出现可能导致治疗失败。
本文介绍了一线治疗药物的选择对长期治疗成功的重要性。
对目前的药物治疗方法进行了综述。
结果/结论：早期药物（拉米夫定或阿德福韦酯）单药治疗与高病毒耐药率相关，联合应用这些药物可降低耐药发生率。最新一代药物（恩替卡韦和替诺福韦）具有很强的抑制病毒复制作用，在初治患者中，恩替卡韦耐药病毒并不常见，替诺福韦也尚未有耐药报道。因此，初治患者首选恩替卡韦或替诺福韦单药治疗。对于耐药乙型肝炎病毒感染患者，应根据病毒耐药基因型/表型选择药物进行联合治疗。虽然联合治疗已在其他患者群体（如失代偿性肝硬化和肝移植后）中得到提倡，但目前尚无数据要求此类患者必须采用联合治疗，任何认为的获益都必须与增加的费用和毒性风险相权衡。
