Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Gastroenterol Hepatol. 2012 Sep;27(9):1432-40. doi: 10.1111/j.1440-1746.2012.07198.x.
In the past decade, broadened therapeutic options of oral direct antiviral agents for the treatment of chronic hepatitis B infection include: Lamivudine, Adefovir Dipivoxil, Telbivudine, Entecavir and Tenofovir Disoproxil Fumarate. These direct oral antiviral agents effectively suppress the replication of the virus and reduce the risk of potential liver-related complications. However, prolonged use of these nucleos(t)ide analogues has been associated with drug resistance that compromises the initial clinical benefits. Moreover, the oncogenic risk of mutations due to prolonged nucleos(t)ide analogue therapy needs to be further investigated by in vitro and in vivo studies. In the current era of potent nucleotide analogues, new data are emerging, we are still facing the pool of patients who have developed resistance to the prior generation of nucleos(t)ide analogues. This paper aims to focus on incidence of antiviral drug resistance and virological breakthrough, prudent selection of initial therapy, on-treatment monitoring for drug resistance and revise treatment strategies for patients with resistant virus.
在过去十年中,慢性乙型肝炎治疗的口服直接抗病毒药物的治疗选择已经拓宽,包括:拉米夫定、阿德福韦酯、替比夫定、恩替卡韦和替诺福韦酯。这些直接口服抗病毒药物能有效抑制病毒复制,降低潜在肝脏相关并发症的风险。然而,这些核苷(酸)类似物的长期使用与耐药性有关,这会影响初始的临床获益。此外,由于长期核苷(酸)类似物治疗导致的突变致癌风险需要通过体外和体内研究进一步研究。在目前强效核苷酸类似物的时代,新的数据不断涌现,我们仍然面临着对前一代核苷(酸)类似物产生耐药的患者群体。本文旨在关注抗病毒药物耐药的发生率和病毒学突破、初始治疗的谨慎选择、耐药治疗监测以及对耐药病毒患者的治疗策略调整。