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在有抗病毒耐药性的病毒学抑制的慢性乙型肝炎患者中,从替诺福韦和核苷类似物治疗转换为替诺福韦单药治疗。

Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance.

机构信息

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

J Med Virol. 2018 Mar;90(3):497-502. doi: 10.1002/jmv.24986. Epub 2017 Nov 14.

DOI:10.1002/jmv.24986
PMID:29077211
Abstract

It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF+NUC combination therapy. This study recruited 76 antiviral-resistant CHB patients showing CVR on TDF+entecavir (ETV) (n = 52), TDF+lamivudine (LAM; n = 14), and TDF+telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF+NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. The step-down strategy of switching from TDF+NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered.

摘要

目前尚不清楚对于接受替诺福韦酯(TDF)与核苷(酸)类似物(NUC)联合治疗后获得完全病毒学应答(CVR)的慢性乙型肝炎(CHB)合并抗病毒耐药患者,如果换用 TDF 单药治疗,其是否能维持 CVR。我们研究了在接受 TDF+NUC 联合治疗后病毒学抑制且具有抗病毒耐药的 CHB 患者停止 NUC 治疗后 CVR 的持续性。该研究共纳入了 76 例在 TDF+恩替卡韦(ETV)(n=52)、TDF+拉米夫定(LAM;n=14)和 TDF+替比夫定(LdT;n=10)联合治疗中获得 CVR 的抗病毒耐药 CHB 患者,这些患者接受 TDF 单药治疗作为降阶梯治疗。基线时,47 例患者为男性,中位年龄为 53.0 岁(范围:30-78 岁);72.3%的病例为乙型肝炎 e 抗原阳性(HBeAg+),23.7%的病例为肝硬化。TDF+NUC 联合治疗的中位时间为 20.8 个月(范围:3-46 个月)。在换用 TDF 单药治疗后的中位随访 24.7 个月(范围:12-48 个月)期间,所有 76 例患者均维持 CVR,无论联合治疗时间、之前 NUC 类型和抗病毒耐药情况如何。在治疗期间未观察到肾功能不全。对于病毒学抑制且具有抗病毒耐药的 CHB 患者,应考虑从 TDF+NUC 联合治疗降阶梯为 TDF 单药治疗的策略。

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引用本文的文献

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Switching from Tenofovir-Based Combination Therapy to Tenofovir Monotherapy in Multidrug-Experienced Chronic Hepatitis B Patients: a 5-Year Experience at Two Centers.从基于替诺福韦的联合治疗转换为多药耐药慢性乙型肝炎患者的替诺福韦单药治疗:两个中心的 5 年经验。
Antimicrob Agents Chemother. 2022 Aug 16;66(8):e0027522. doi: 10.1128/aac.00275-22. Epub 2022 Jul 13.
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KASL clinical practice guidelines for management of chronic hepatitis B.《慢性乙型肝炎管理的KASL临床实践指南》
Clin Mol Hepatol. 2019 Jun;25(2):93-159. doi: 10.3350/cmh.2019.1002. Epub 2019 Jun 12.