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拉米夫定耐药的阿德福韦酯治疗应答不佳的慢性乙型肝炎患者中应用替诺福韦的挽救治疗。

Tenofovir-based rescue therapy in chronic hepatitis B patients with suboptimal responses to adefovir with prior lamivudine resistance.

机构信息

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

出版信息

J Med Virol. 2015 Sep;87(9):1532-8. doi: 10.1002/jmv.24201. Epub 2015 May 4.

Abstract

We evaluated the efficacy of tenofovir (TDF)-based rescue therapy and compared the outcomes of TDF monotherapy and TDF-based nucleoside analog (NA) combination therapy in patients with suboptimal response (SOR) to adefovir (ADV) with or without NAs in lamivudine (LAM)-resistant chronic hepatitis B. All study subjects received ADV with or without NAs due to prior LAM resistance, and were then switched to TDF-based rescue therapy due to SOR (hepatitis B virus DNA >20 IU/ml after at least 6 months of therapy). A total of 125 patients were eligible. The overall cumulative proportion of complete virologic response (CVR) was 64 of 74 patients (86.5%) at 48 weeks of treatment. During the follow-up period of 48 weeks, there was no significant difference in CVR rate (P = 0.750) between the TDF monotherapy (n = 18) and the TDF with NA groups (n = 107). Patients with ADV genotypic mutations showed inferior antiviral responses to TDF compared with the patients without ADV genotypic mutations, but this was not statistically significant (P = 0.069). Partial virological response to prior ADV therapy showed higher CVR rates compared to patients with non-response at 12 weeks (P = 0.013), but there was no significant difference after 24 (P = 0.076) and 48 weeks (P = 0.198) of treatment. TDF monotherapy is as effective as TDF plus NA combination therapy in patients with SOR to ADV-based rescue therapy and LAM resistance. TDF, with or without NAs, was effective even in cases of ADV resistance.

摘要

我们评估了替诺福韦(TDF)为基础的挽救治疗的疗效,并比较了在拉米夫定(LAM)耐药慢性乙型肝炎患者中,阿德福韦(ADV)耐药或无耐药核苷类似物(NA)联合治疗基础上发生治疗应答不佳(SOR)后,TDF 单药治疗和 TDF 为基础的 NA 联合治疗的结局。所有研究对象均因先前的 LAM 耐药而接受 ADY 加或不加 NAs 治疗,随后因 SOR(治疗至少 6 个月后乙型肝炎病毒 DNA >20 IU/ml)而转换为 TDF 为基础的挽救治疗。共有 125 名患者符合条件。在治疗 48 周时,74 名患者中共有 64 名(86.5%)获得完全病毒学应答(CVR)。在 48 周的随访期间,TDF 单药治疗(n=18)和 TDF+NA 组(n=107)的 CVR 率无显著差异(P=0.750)。ADV 基因型突变患者的抗病毒应答不如无 ADV 基因型突变患者,但无统计学意义(P=0.069)。与 12 周无应答患者相比,先前 ADV 治疗的部分病毒学应答患者的 CVR 率更高(P=0.013),但在 24 周(P=0.076)和 48 周(P=0.198)时无显著差异。TDF 单药治疗与 TDF+NA 联合治疗在 ADV 挽救治疗和 LAM 耐药患者中同样有效。TDF 联合或不联合 NAs 治疗对 ADV 耐药患者也有效。

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