恩替卡韦+替诺福韦与拉米夫定/替比夫定+阿德福韦治疗慢性

StephenW

Entecavir+tenofovir vs. Lamivudine/Telbivudine+adefovir in Chronic Hepatitis B Patients With Prior Suboptimal Response
Hyun Young Woo  1   2 , Jun Yong Park  3 , Si Hyun Bae  4 , Chang Wook Kim  4 , Jae Young Jang  5 , Won Young Tak  6 , Dong Joon Kim  7   8 , In Hee Kim  9 , Jeong Heo  1   2 , Sang Hoon Ahn  3
Affiliations
Affiliations

    1
    Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea.
    2
    Medical Research Institute, Pusan National University Hospital, Busan, Korea.
    3
    Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
    4
    Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    5
    Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea.
    6
    Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
    7
    Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
    8
    Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.
    9
    Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University College of Medicine, Chonju, Korea.

    PMID: 32460460 DOI: 10.3350/cmh.2019.0044n

Abstract

Background/aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.

Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.

Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.

Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

Keywords: Adefovir; Antiviral drug resistance; Lamivudine; Tenofovir; Entecavir.
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StephenW

恩替卡韦+替诺福韦与拉米夫定/替比夫定+阿德福韦治疗慢性乙型肝炎先有次优反应的患者
Hyun Young Woo 1 2，Jun Yong Park 3，Si Hyun Bae 4，Chang Wook Kim 4，Jae Young Jang 5，Won Young Tak 6，Dong Joon Kim 7 8，In Hee Kim 9，Jeong Heo 1 2，Sang Hoon Ahn 3
隶属关系
隶属关系

    1个
    釜山国立大学医学院内科系，釜山，韩国。
    2
    韩国釜山釜山国立大学医院医学研究所。
    3
    延世大学医学院内科，韩国首尔。
    4
    韩国天主教大学医学院内科，韩国首尔。
    5
    淳春市大学医学院消化病研究所消化疾病研究所消化内科，韩国首尔。
    6
    韩国大邱庆北国立大学医学院内科。
    7
    韩国春川市哈林大学医学院内科。
    8
    韩国春川市哈林大学肝与消化系统疾病研究所。
    9
    韩国全州市春北国立大学医学院春北国立大学医院内科。

    PMID：32460460 DOI：10.3350 / cmh.2019.0044n

抽象

背景/目的：拉米夫定或替比夫定加阿德福韦（LAM / LdT + ADV）抢救疗法的亚最佳反应在LAM耐药性乙型肝炎病毒（HBV）感染患者中很常见。我们比较了改用恩替卡韦加替诺福韦（ETV + TDF）的患者与维持LAM / LdT + ADV的患者。

方法：这项前瞻性随机对照试验检查了91例接受LAM / LdT + ADV治疗LAM耐药性HBV至少24周后血清HBV DNA水平高于60 IU / mL的患者。患者被随机分配接受新治疗（ETV + TDF，n = 45）或接受相同治疗（LAM / LdT + ADV，n = 46）48周。排除基线ADV耐药的患者。

结果：与LAM / LdT + ADV组相比，ETV + TDF组的病毒学应答患者更多（42/45 [93.33％] vs. 3/46 [6.52％]，P <0.001），且平均降低幅度更大基线时血清HBV DNA水平升高（-4.16 vs.-0.37 log10 IU / mL，P <0.001）。多因素分析表明，高基线HBV DNA水平（P = 0.005）和LAM / LdT + ADV维持治疗（P = 0.001）与病毒学应答呈负相关。在第48周，ETV + TDF组中清除了其他ADV或ETV相关突变，但LAM / LdT + ADV组中4.3％的患者中存在此类突变（P = 0.106）。两组的不良事件发生率相似。

结论：与LAM / LdT + ADV联合治疗相比，ETV + TDF联合治疗对LAM耐药的HBV患者的应答较LAM / LdT + ADV差，无论HBV基因型耐药情况如何（NCT01597934） ）。

关键字：阿德福韦；抗病毒药物耐药性；拉米夫定;替诺福韦;恩替卡韦。