核苷类药物治疗慢性乙型肝炎的进展

Progress in Nucleoside and Nucleotide Analogue Therapy for Chronic Hepatitis B

目的:核苷类药物(nucleoside and nucleotide analogs,NAs)是临床最常用的一大类抗乙型肝炎病毒药物,笔者概述常用NAs特点及其耐药的管理、经济评估以及抗病毒治疗指征等方面的进展。方法:在Pub Med、Cochrane Central、EMbase英文数据库和CNKI、Wan Fang Data等中文数据库检索信息,搜集了慢性乙型肝类(CHB)流行病学、NAs治疗CHB的临床试验及荟萃分析、NAs耐药性、NAs治疗CHB的经济评估、CHB治疗指南(美国、欧洲、亚太及中华肝病学会)等相关文献并总结分析。结果与结论:目前恩替卡韦(ETV)和替诺福韦酯(TDF)因其强效、不易产生耐药被指南推荐为一线用药,其余NAs均被建议在无法使用ETV和TDF时使用。耐药是NAs治疗过程中必须重视的一大问题,可导致疾病进展、增加治疗的难度与成本。目前的研究揭示了相关耐药位点与产生耐药的模式,在临床具体应用中,应通过加强教育、合理选择用药、重视监测、及时补救治疗等手段减少和应对耐药。在我国CHB的长期治疗中,与TDF以外的NAs相比,ETV具有较好的成本效益。临床上需严格掌握抗病毒治疗的指征,避免不必要用药的同时,及时对符合治疗指征的患者抗病毒治疗并进行监测。

Objective： The nucleoside and nucleotide analogues （NAs） are a large group of commonly used antiviral drugs for hepatitis B viral （HBV） infection. This review generalizes the updated progress of NAs about their characteristics, the management of drug resistances, economic evaluation, and indication of antiviral treatment. Methods： Information was retrieved from PubMed, the Cochrane Central, EMbase, CNKI, and WanFang databases, as wel as the practice guidelines on the treatment of chronic hepatitis B （CHB）. The epidemiology of CHB, clinical trials and meta-analysis of NAs for the treatment of CHB, the drug resistance of NAs and their economic evaluation were summarized. Results and Conclusion： Currently entecavir and tenofovir disoproxil monotherapy are recommended as the first-line drugs by practice guidelines due to their potent antiviral efficacy and low incidence of viral resistance. Other NAs are proposed in HBV patients who are unsuitable for being administered with entecavir and tenofovir. Drug resistance is the main concern with NA treatment, which can lead to disease progression, dififculty in treatment, and higher medication costs. Current research has uncovered common drug resistant mutants as wel as the mechanisms underlying emergence of resistance. In the clinical use of HBV antiviral drugs, we need to enhance education, rational y select drugs, closely monitor the emergence of drug resistance in patients , and optimize treatment regimens to avoid or minimize drug resistance. Entecavir is the most cost-effective option when compared with lamivudine, adefovir, and telbivudine for CHB patients in China. While patients with appropriate clinical indications should be treated with antiviral agents promptly, close monitoring is required and unnecessary usage of NA drugs should be avoided.