INSERM, U1052, Cancer Research Center of Lyon, 69003 Lyon, France.
J Hepatol. 2012;56 Suppl 1:S112-22. doi: 10.1016/S0168-8278(12)60012-9.
Antiviral therapy of chronic hepatitis B remains a clinical challenge. The primary goal of therapy is to prevent liver disease progression. Because of the mechanism of viral persistence in infected hepatocytes, long-term antiviral therapy is needed in the majority of patients. Incomplete viral suppression and emergence of drug resistance is a major concern. The correct choice of a first-line potent therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance, such as entecavir and tenofovir, have significantly lower rates of resistance when compared with those with a low barrier to resistance such as lamivudine, adefovir, or telbivudine. Management of treatment failure requires a precise clinical and accurate virologic monitoring as well as an early treatment intervention with appropriate complementary drugs with respect to their cross-resistance profile. Long-term surveillance for treatment efficacy and possible emergence of drug resistance is necessary for those patients who have been sequentially treated with multiple antivirals. Finally, the identification of novel treatment targets remains a major research challenge to improve the efficacy of current antiviral therapy.
慢性乙型肝炎的抗病毒治疗仍然是一个临床挑战。治疗的主要目标是预防肝病进展。由于病毒在感染的肝细胞中持续存在的机制，大多数患者需要长期抗病毒治疗。不完全的病毒抑制和耐药性的出现是一个主要关注点。正确选择一线强效治疗方法以实现持续的长期病毒复制抑制，为预防治疗失败和耐药性提供了最佳机会。临床研究表明，与耐药屏障低的药物（如拉米夫定、阿德福韦或替比夫定）相比，耐药屏障高的药物（如恩替卡韦和替诺福韦）的耐药率显著降低。治疗失败的管理需要精确的临床和准确的病毒学监测，以及早期治疗干预，同时考虑到其交叉耐药谱的适当互补药物。对于那些已经接受多种抗病毒药物序贯治疗的患者，需要长期监测治疗效果和可能出现的耐药性。最后，确定新的治疗靶点仍然是提高现有抗病毒治疗效果的主要研究挑战。
