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乙型肝炎联合治疗的益处与风险。

Benefits and risks of combination therapy for hepatitis B.

作者信息

Terrault Norah A

机构信息

Departments of Medicine and Surgery, University of California San Francisco, San Francisco, CA 94143-0538, USA.

出版信息

Hepatology. 2009 May;49(5 Suppl):S122-8. doi: 10.1002/hep.22921.

Abstract

In successful antiviral therapy of hepatitis B, drug combinations, particularly combinations without cross-resistance, can delay or prevent the emergence of drug-resistant mutants. Because drug-resistant mutants are archived and may limit future therapeutic options, prevention is important for long-term therapeutic efficacy. Additionally, combining drugs may achieve synergistic or additive antiviral effects compared with single drug therapy. Undesirable aspects of combination therapy include higher treatment costs and possibly lower adherence rates (due to pill number or complexity of regimen). Potentially harmful effects of combination therapy include higher rates of side effects, reduced efficacy due to drug competition, and the risk of multidrug-resistant hepatitis B virus (HBV) if combination therapy is insufficient to prevent resistance. Combination therapy has been shown to reduce the rate of drug resistance in chronic hepatitis B, but only when drugs with a low barrier to resistance are used (lamivudine, adefovir). Combination therapies may achieve greater degrees of HBV DNA suppression, but this has not been associated with higher rates of seroconversion (hepatitis B e antigen or hepatitis B surface antigen) compared to single drug therapy. The benefit of combination therapy has yet to be demonstrated with agents that are associated with a high barrier to resistance (tenofovir, entecavir). The use of combination therapy is recommended in specific patient groups: those with decompensated cirrhosis, those coinfected with human immunodeficiency virus and HBV who are on antiretroviral therapy, those who have undergone liver transplantation, and those with drug-resistant HBV infection. There is insufficient evidence to recommend combination therapy as first-line therapy for all patients with chronic hepatitis B.

摘要

在成功的乙型肝炎抗病毒治疗中,药物联合使用,特别是无交叉耐药性的联合用药,可延缓或预防耐药突变体的出现。由于耐药突变体被存档且可能限制未来的治疗选择,因此预防对于长期治疗效果很重要。此外,与单一药物治疗相比,联合用药可能会产生协同或相加的抗病毒效果。联合治疗的不利方面包括治疗成本较高以及依从率可能较低(由于药丸数量或治疗方案的复杂性)。联合治疗的潜在有害影响包括副作用发生率较高、因药物竞争导致疗效降低,以及如果联合治疗不足以预防耐药则有产生多重耐药乙型肝炎病毒(HBV)的风险。联合治疗已被证明可降低慢性乙型肝炎的耐药率,但仅在使用耐药门槛较低的药物(拉米夫定、阿德福韦)时才有效。联合治疗可能会实现更高程度的HBV DNA抑制,但与单一药物治疗相比,这并未与更高的血清学转换率(乙肝e抗原或乙肝表面抗原)相关联。联合治疗对耐药门槛较高的药物(替诺福韦、恩替卡韦)的益处尚未得到证实。在特定患者群体中推荐使用联合治疗:失代偿期肝硬化患者、接受抗逆转录病毒治疗的人类免疫缺陷病毒和HBV合并感染患者、肝移植患者以及耐药HBV感染患者。没有足够的证据推荐将联合治疗作为所有慢性乙型肝炎患者的一线治疗方法。

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