评价拉米夫定加阿德福韦酯替代替诺福韦酯单药治疗拉米夫

StephenW

PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018.
Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients.
Lee HJ1, Kim SJ2, Kweon YO3, Park SY3, Heo J4, Woo HY4, Hwang JS2, Chung WJ2, Lee CH5, Kim BS5, Suh JI6, Tak WY3, Jang BK2.
Author information

1
    Department of Internal Medicine, Yeungnam University College of Medicine Daegu, South Korea.
2
    Department of Internal Medicine, Keimyung University school of Medicine, Daegu, South Korea.
3
    Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, South Korea.
4
    Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea.
5
    Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea.
6
    Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, South Korea.

Abstract
BACKGROUND:

The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.
METHODS:

In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.
RESULTS:

Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84-5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000).
CONCLUSIONS:

Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.
TRIAL REGISTRATION:

ClinicalTrials.gov NCT01732367.

PMID:
    29329305
DOI:
    10.1371/journal.pone.0190581

StephenW

PLoS One。 2018年1月12日; 13（1）：e0190581。 doi：10.1371 / journal.pone.0190581。 eCollection 2018年。
评价拉米夫定加阿德福韦酯替代替诺福韦酯单药治疗拉米夫定耐药稳定期乙型肝炎患者的疗效。
Lee HJ1，Kim SJ2，Kweon YO3，Park SY3，Heo J4，Woo HY4，Hwang JS2，Chung WJ2，Lee CH5，Kim BS5，Su JI6，Tak WY3，Jang BK2。
作者信息

1
    韩国大邱岭南大学医学部内科。
2
    韩国大邱市启明大学医学部内科。
3
    韩国大邱庆北大学医学部内科。
4
    韩国釜山釜山国立大学医学院内科。
五
    韩国大邱天主教大学内科医学部，韩国大邱。
6
    东国大学医学院内科，韩国庆州。

抽象
背景：

（LAM）联合阿德福韦酯（ADV）联合治疗（稳定转换）治疗抗LAM慢性乙型肝炎（CHB）和检测不到乙型肝炎病毒（HBV）DNA的患者中转用替诺福韦酯替诺福韦（TDF）单药治疗的疗效不清楚。
方法：

在这项非劣效性试验中，开始LAM + ADV联合治疗6个月以上的LAM耐药CHB和检测不到的血清HBV DNA（<20 IU / mL）的患者随机（1：2）或者继续联合治疗LAM + ADV组，n = 58）或转为TDF单药治疗（TDF组，n = 111）。随访时间为12周，进行血清生化检测和HBV DNA检测，共96周。本研究的主要终点为96周病毒再激活患者的比例。
结果：

参与本研究的CHB患者（n = 169）包括74例代偿性肝硬化患者。总共有9名患者（LAM + ADV组4名和TDF组5名）从研究中退出。平均随访96周后，LAM + ADV组的HBV再激活比例为6.8％（4/58），TDF组为4.5％（5/111），采用意向治疗分析（差异，-2.3％; 95％CI，-9.84-5.24％）。任何一组的受试者均未经历基于每个方案分析的病毒再激活。没有观察到严重的不良反应。在治疗前后估计肾小球滤过率（eGFR）的亚组分析中，仅在TDF组肝硬化组中观察到eGFR下降（85.22比79.83 mL / min / 1.73 m2，p = 0.000）。
结论：

与使用LAM + ADV联合治疗LAM耐药CHB和检测不到HBV DNA的患者相比，稳定转换至TDF单药治疗在96周时产生了非劣效的结果。然而，TDF单药治疗肝硬化患者需要密切关注肾功能。
试用注册：

ClinicalTrials.gov NCT01732367。

结论：
    29329305
DOI：
    10.1371 / journal.pone.0190581