基于替诺福韦的多药耐药性慢性乙型肝炎联合治疗或单药治

StephenW

Tenofovir-based combination therapy or monotherapy for multi-drug resistant chronic hepatitis B: Long-term data from a multicenter cohort study
Hyung Joon Yim  1 , Sang Jun Suh  1 , Young Kul Jung  1 , Seong Gyu Hwang  2 , Yeon Seok Seo  1 , Soon Ho Um  1 , Sae Hwan Lee  3 , Young Seok Kim  3 , Jae Young Jang  3 , In Hee Kim  4 , Hyoung Su Kim  5 , Ji Hoon Kim  1 , Young Sun Lee  1 , Eileen L Yoon  6 , Myeong Jun Song  7 , Jun Yong Park  8
Affiliations
Affiliations

    1
    Department of Internal Medicine, Korea University Medical College, Seoul, Korea.
    2
    Department of Internal Medicine, CHA University School of Medicine, Seongnam, Korea.
    3
    Department of Internal Medicine, Soonchunhyang University Medical College, Seoul, Korea.
    4
    Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.
    5
    Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea.
    6
    Department of Internal Medicine, Inje University College of Medicine, Seoul, South Korea.
    7
    Department of Internal Medicine, the Catholic University of Korea, College of Medicine, Seoul, Korea.
    8
    Department of Internal Medicine, Yonsei University Medical College, Seoul, Korea.

    PMID: 32706461 DOI: 10.1111/jvh.13363

Abstract

The treatment of multidrug resistant (MDR) chronic hepatitis B (CHB) is challenging. Herein, we report a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)-based therapy for MDR CHB in a real-life setting. The inclusion criteria comprised patients with resistance to more than two nucleos(t)ide analogue (NA) classes and hepatitis B virus (HBV) DNA level of ≥200 IU/mL. The primary end-point was virologic response (VR), defined as undetectable HBV DNA (<20 IU/mL) after 60 months. A total of 236 patients met the inclusion criteria. The mean HBV DNA level was 4.16±1.44 log IU/mL; 26.7% of patients had liver cirrhosis. Before the initiation of TDF, 33.5%, 44.9%, and 21.6% of patients had mutations resistant to L-NA+adefovir, L-NA+entecavir (ETV), and L-NA+adefovir+ETV, respectively. A total of 184 patients received TDF-based combination therapy [TDF+ETV (n=178) or TDF+L-NA (n=6)], and 52 patients received TDF monotherapy. In the entire cohort, the VR rates were 77.2%, 89.9%, and 92.2% at 12, 36, and 60 months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs. 80.4%, P=0.533), 36 (89.8% vs. 90.3%, P=1.000), or 60 (92.9% vs. 87.5%, P=0.499) months. Also there was no significant difference in the cumulative VR rates for 5 years between the treatment groups (P=0.910). Newly developed antiviral resistance was not observed.TDF-based therapy was effective for the treatment of MDR CHB. The efficacy of TDF monotherapy was not different from that of the TDF-based combination therapy.

Keywords: Chronic hepatitis B; Multi-drug resistance; Tenofovir; Therapy.

StephenW

基于替诺福韦的多药耐药性慢性乙型肝炎联合治疗或单药治疗：来自多中心队列研究的长期数据
Hyung Joon Yim 1，Sang Jun Suh 1，Young Kul Jung 1，Seong Gyu Hwang 2，Yeon Seok Seo 1，Soon Ho Um 1，Sae Hwan Lee 3，Young Seok Kim 3，Jae Young Jang 3，In Hee Kim 4， Hyoung Su Kim 5，Ji Hoon Kim 1，Young Sun Lee 1，Eileen L Yoon 6，Myeong Jun Song 7，Jun Yong Park 8
隶属关系
隶属关系

    1个
    高丽大学医学院内科，韩国首尔。
    2
    韩国城南大学CHA大学医学院内科。
    3
    韩国首尔不久春阳大学医学院内科。
    4
    韩国全州市春北国立大学医学院内科。
    5
    哈里姆大学医学院内科，韩国首尔。
    6
    韩国首尔仁济大学医学院内科。
    7
    韩国天主教大学内科，韩国首尔医学院。
    8
    延世大学医学院内科，韩国首尔。

    PMID：32706461 DOI：10.1111 / jvh.13363

抽象

耐多药（MDR）慢性乙型肝炎（CHB）的治疗具有挑战性。在此，我们报告了一项多中心前瞻性队列研究，用于评估在现实生活中基于替诺福韦富马酸替诺福韦酯（TDF）的MDR CHB治疗的评估。纳入标准包括对两种以上核苷酸类似物（NA）耐药且乙肝病毒（HBV）DNA水平≥200 IU / mL的患者。主要终点是病毒学应答（VR），定义为60个月后无法检测到的HBV DNA（<20 IU / mL）。共有236名患者符合纳入标准。 HBV DNA平均水平为4.16±1.44 log IU / mL； 26.7％的患者患有肝硬化。在开始TDF之前，分别有33.5％，44.9％和21.6％的患者具有对L-NA +阿德福韦，L-NA +恩替卡韦（ETV）和L-NA +阿德福韦+ ETV耐药的突变。共有184例患者接受了基于TDF的联合治疗[TDF + ETV（n = 178）或TDF + L-NA（n = 6）]，而52例患者接受了TDF单一疗法。在整个队列中，第12、36和60个月的VR发生率分别为77.2％，89.9％和92.2％。联合疗法和单一疗法组之间的VR率在12（76.2％vs. 80.4％，P = 0.533），36（89.8％vs. 90.3％，P = 1.000）或60（92.9％vs. 87.5％，P = 0.499）个月。同样，治疗组之间5年的累积VR率也无显着差异（P = 0.910）。没有观察到新开发的抗病毒耐药性。基于TDF的疗法对MDR CHB的治疗有效。 TDF单一疗法的疗效与基于TDF的联合疗法无异。

关键字：慢性乙型肝炎；多药耐药性；替诺福韦;治疗。