AASLD2018[264]一项随机安慰剂对照试验 替诺福韦地索普西富马

StephenW

264
A Randomized Placebo-Controlled Trial of
Tenofovir Disoproxil Fumarate in Chronic
Hepatitis B Patients with Minimally Elevated
Aminotransferase
Yao-Chun Hsu1, Chi-Yi Chen2, Chun-Ying Wu3, I-Wei Chang4,
Teng-Yu Lee5, Chi-Yang Chang6, Ming-Jong Bair7, Jyh-Jou
Chen8, Ming-Shiang Wu9, Chieh-Chang Chen9, Cheng-Hao
Tseng10, Wen-Hui Ku11, Lien-Juei Mou12 and Jaw-Town Lin6,
(1)I-Shou University, (2)Chia-Yi Christian Hospital, Chia Yi,
Taiwan, (3)Taipei Veterans General Hospital, (4)Taipei Medical
University Hospital, (5)Taichung Veterans General Hospital,
(6)Fu-Jen Catholic University Hospital, (7)Mackay Memorial
Hospital-Taitung Branch, (8)Chi-Mei Medical Center, (9)
National Taiwan University Hospital, (10)E-Da Hospital, (11)
Taipei Pathology Institutes, (12)Tainan Municipal Hospital
Background: Whether antiviral therapy is indicated in chronic
hepatitis B (CHB) patients with mild clinical hepatitis remains
controversial. Definitive evidence of therapeutic efficacy
has been lacking in patients with minimally raised alanine
aminotransferase (ALT). We aimed to clarify whether tenofovir
disoproxil fumarate (TDF) could prevent disease progression
in CHB patients with minimally raised ALT. Methods: This is
a multicenter randomized triple-blind placebo-controlled trial
from Taiwan. We enrolled a total of 160 CHB patients whose
serum ALT ranged 1-2 folds the upper limit of normal (ULN) with
viral DNA >2,000 IU/mL in the preceding year, and randomized
them to receive either TDF (n=80) or placebo (n=80) for 3
years. Patients with baseline cirrhosis were ineligible. The
primary outcomes were histological progression of liver
fibrosis and necroinflammation as evaluated by the Knodell
and Ishak scoring systems. Results: As of May 28, 2018, 65
TDF and 67 placebo receivers have completed the 3-year trial
and undergone paired liver biopsy. The results of these 132
patients were herein presented. The two study groups (TDF
vs. placebo) were comparable with similar characteristics at
baseline, such as (median, IQR) age (45, [39-54] vs. 43, [38-
51] years), viral DNA (5.32, [4.30-6.47] vs. 5.32, [4.39-6.29] log
IU/mL), and ALT levels (53, [46-63] vs. 52, [46-66] U/L). After
3 years of trial, liver fibrosis progressed (≥ 1-unit increase in
the Ishak stage) in 15 (23.1%) and 30 (44.8%) patients in the
TDF and placebo receivers, respectively (P=0.01). Cirrhosis
(Ishak stage 5 or 6) was documented in 2 (3.1%) and 9
(13.4%) patients in the TDF and placebo groups, respectively
(P=0.05). Hepatic necroinflammation improved (≥ 2-point
decrease in the Knodell necroinflammatory score) in 24
(36.9%) TDF and 18 (26.9%) placebo receivers, respectively
(P=0.26). Furthermore, the TDF receivers achieved higher
rates of undetectable HBV DNA level (n=53, 81.5% vs. n=9,
13.4%; P<0.001) and normalized ALT level (n=49, 75.4%
vs. n=35, 52.2%; P=0.007) than their placebo counterparts.
Hepatocellular carcinoma occurred in 2 TDF and 1 placebo
users, respectively (P=1.0). Conclusion: Antiviral treatment
using TDF reduces the risk of liver fibrosis progression in
CHB patients with minimally raised ALT (ClinicalTrials.gov
identifier: NCT01522625).

StephenW

264
一项随机安慰剂对照试验
替诺福韦地索普西富马酸盐治疗慢性乙型肝炎
乙型肝炎患者最低升高
转氨酶
Hang-Chun Hsu1，陈志毅2，吴春英3，I-Wei Chang4，
Teng-Yu Lee5，Chi-Yang Chang6，Ming-Jong Bair7，Jyh-Jou
陈8，吴明祥9，陈杰昌9，程浩
Tseng10，Wen-Hui Ku11，Lien-Juei Mou12和Jaw-Town Lin6，
（1）I-Shou大学，（2）Chia-Yi基督教医院，Chia Yi，
台湾，（3）台北退伍军人总医院，（4）台北医疗
大学医院，（5）台中退伍军人总医院，
（6）辅仁天主教大学医院，（7）麦凯纪念馆
医院 - 台东分院，（8）奇美医疗中心，（9）
国立台湾大学医院，（10）E-Da医院，（11）
台北市病理研究所，（12）台南市立医院
背景：抗病毒治疗是否适用于慢性病
乙肝（CHB）患者轻度临床肝炎仍然存在
争议。治疗效果的确切证据
一直缺乏丙氨酸最少的患者
氨基转移酶（ALT）。我们旨在澄清是否是替诺福韦
disoproxil fumarate（TDF）可以预防疾病进展
在CHB患者中ALT升高最低。方法：这是
一项多中心随机三盲安慰剂对照试验
来自台湾我们招募了160名CHB患者
血清ALT为正常上限（ULN）的1-2倍
病毒DNA在前一年> 2,000 IU / mL，随机分组
他们接受TDF（n = 80）或安慰剂（n = 80）3
年份。基线肝硬化患者不合格。该
主要结果是肝脏的组织学进展
由Knodell评估的纤维化和坏死性炎症
和Ishak得分系统。结果：截至2018年5月28日，65
TDF和67名安慰剂接收者已完成为期3年的试验
并进行配对肝活检。结果这132个
患者在此呈现。两个研究组（TDF
与安慰剂相比，具有相似的特征
基线，如（中位数，IQR）年龄（45，[39-54]对43，[38-
51]年，病毒DNA（5.32，[4.30-6.47] vs. 5.32，[4.39-6.29] log
IU / mL）和ALT水平（53，[46-63]对比52，[46-66] U / L）。后
3年的试验，肝纤维化进展（≥1单位增加）
Ishak阶段）在15名（23.1％）和30名（44.8％）患者中
TDF和安慰剂接收器分别为（P = 0.01）。硬化
（Ishak阶段5或6）记录在2（3.1％）和9
（13.4％）患者分别为TDF和安慰剂组
（P = 0.05）。肝脏坏死性炎症改善（≥2分
在24中降低Knodell坏死性炎症评分
（36.9％）TDF和18（26.9％）安慰剂接收器
（P = 0.26）。此外，TDF接收器实现了更高的性能
无法检测HBV DNA水平的比率（n = 53,81.5％对n = 9，
13.4％; P <0.001）和ALT水平正常化（n = 49,75.4％）
与n = 35,52.2％; P = 0.007）比他们的安慰剂对应物。
肝细胞癌发生在2个TDF和1个安慰剂中
用户，分别（P = 1.0）。结论：抗病毒治疗
使用TDF降低了肝纤维化进展的风险
ALB最低升高的CHB患者（ClinicalTrials.gov
标识符：NCT01522625）。