Keeffe Emmet B, Dieterich Douglas T, Pawlotsky Jean-Michel, Benhamou Yves
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Clin Gastroenterol Hepatol. 2008 Mar;6(3):268-74. doi: 10.1016/j.cgh.2007.12.043.
Licensed oral agents for antiviral therapy in patients with chronic hepatitis B virus (HBV) infection include lamivudine, adefovir, entecavir, and telbivudine. Emtricitabine, tenofovir, and the combination of tenofovir plus emtricitabine in 1 tablet, which are licensed for the treatment of human immunodeficiency virus infection, are additional off-label options for treating HBV infection. Preventing HBV antiviral drug resistance to nucleoside/nucleotide analogues and appropriate management when resistance occurs has become a major focus in the management of chronic hepatitis B. HBV antiviral drug resistance may be best prevented by using an agent or combination of agents with a high genetic barrier to resistance, and 2 potent nucleoside and nucleotide drugs with different resistance profiles may prove to be the optimal first-line treatment for chronic hepatitis B. Frequent assessment of quantitative serum HBV DNA remains the best approach to early detection of resistance, and antiviral therapy should be modified as soon as resistance is detected. Results from several clinical trials have shown that the addition or substitution of newer antiviral agents can restore suppression of viral replication, normalize alanine aminotransferase levels, and reverse histologic progression in patients with resistance to lamivudine, but little information exists regarding the long-term benefits of second-line treatment regimens. Despite the substantial advances in treatment made to date, new agents with novel viral targets will be needed for patients who ultimately may fail second- or third-line therapy.
用于慢性乙型肝炎病毒（HBV）感染患者抗病毒治疗的口服许可药物包括拉米夫定、阿德福韦、恩替卡韦和替比夫定。恩曲他滨、替诺福韦以及将替诺福韦与恩曲他滨组合在一片剂中的药物，这些药物被许可用于治疗人类免疫缺陷病毒感染，是治疗HBV感染的额外非标签选择。预防HBV对抗核苷/核苷酸类似物的抗病毒耐药性以及耐药发生时的适当管理已成为慢性乙型肝炎管理的主要重点。使用对耐药具有高遗传屏障的一种药物或药物组合可能是预防HBV抗病毒耐药性的最佳方法，两种具有不同耐药谱的强效核苷和核苷酸药物可能被证明是慢性乙型肝炎的最佳一线治疗方法。频繁评估血清HBV DNA定量仍然是早期检测耐药性的最佳方法，一旦检测到耐药性，就应修改抗病毒治疗方案。多项临床试验结果表明，添加或替换更新的抗病毒药物可以恢复对病毒复制的抑制，使丙氨酸转氨酶水平正常化，并逆转对拉米夫定耐药患者的组织学进展，但关于二线治疗方案的长期益处的信息很少。尽管迄今为止在治疗方面取得了重大进展，但对于最终可能在二线或三线治疗中失败的患者，仍需要具有新型病毒靶点的新药物。
