别加-软肝对恩替卡韦治疗的慢性乙型肝炎患者纤维化退化的

StephenW

Synergistic Effect of Biejia-Ruangan on Fibrosis Regression in Patients With Chronic Hepatitis B Treated With Entecavir: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial
Guanghua Rong  1 , Yongping Chen  2 , Zujiang Yu  3 , Qin Li  4 , Jingfeng Bi  5 , Lin Tan  6 , Dedong Xiang  7 , Qinghua Shang  8 , Chunliang Lei  9 , Liang Chen  10 , Xiaoyu Hu  11 , Jing Wang  12 , Huabao Liu  13 , Wei Lu  14 , Yan Chen  1 , Zheng Dong  1 , Wenlin Bai  1 , Eric M Yoshida  15 , Nahum Mendez-Sanchez  16 , Ke-Qin Hu  17 , Xingshun Qi  18 , Yongping Yang  1
Affiliations
Affiliations

    1
    Department of Liver Diseases of Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
    2
    Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
    3
    Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
    4
    Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China.
    5
    Department of Clinical & Translational Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
    6
    Liver Disease Department, Fuyang 2nd People's Hospital, Fuyang, Anhui Province, China.
    7
    Department of Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing, China.
    8
    Therapeutic Center for Liver Disease, the 88th Hospital of PLA, Taian, Shandong Province, China.
    9
    Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China.
    10
    Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China.
    11
    National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
    12
    Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
    13
    Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China.
    14
    Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China.
    15
    Division of Gastroenterology, Vancouver General Hospital, Vancouver, British Columbia, V6T1Z4 Canada.
    16
    Liver Research Unit Medica Sur Clinic & Foundation & Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
    17
    Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, CA, USA.
    18
    Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China.

    PMID: 32437567 DOI: 10.1093/infdis/jiaa266

Abstract

Background and aims: Long-term nucleos(t)ide analogues (NAs) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an anti-fibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs.

Methods: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5mg per day) plus BR (2g three times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥1 point by the Ishak Fibrosis Stage (IFS).

Results: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 week treatment was significantly higher in ETV+BR group (40% versus 31.8%, P=0.0069). Among 388 patients with cirrhosis (i.e., IFS ≥5) at baseline, the rate of cirrhosis reversal (i.e., IFS ≤4) was significantly higher in ETV+BR group (41.5% versus 30.7%, P=0.0103).

Conclusions: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression.

Keywords: Entecavir; Hepatitis B; Liver cirrhosis; Liver fibrosis; Traditional Chinese Medicine.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America

StephenW

别加-软肝对恩替卡韦治疗的慢性乙型肝炎患者纤维化退化的协同作用：多中心，随机，双盲，安慰剂对照试验
光荣1，陈永平2，祖江3，秦丽4，景丰壁5，林滩6，德栋乡7，清华上8，春亮雷9，梁晨10，胡小玉11，王景12，刘华宝13，韦路14，严晨1，郑东1，文林白1，吉田埃里克·M，吉卜力·纳胡姆·门德斯·桑切斯16，胡克勤17，兴顺旗18，杨永平1
隶属关系
隶属关系

1个
中国人民解放军总医院第五医疗中心中国人民解放军总医院肝病科，北京。
2
温州医科大学附属第一医院肝病研究中心传染病与肝病科，浙江温州。
3
郑州大学第一附属医院感染科，河南郑州。
4
中国福建省福州市，福州传染病医院。
5
中国人民解放军总医院第五医疗中心临床转化医学科，北京。
6
阜阳市第二人民医院肝病科，安徽省阜阳市。
7
第三军医大学西南医院感染科，重庆。
8
解放军第八十八医院肝病治疗中心，山东泰安。
9
中国广东省广州市广州市第八人民医院。
10
上海市公共卫生临床中心肝病科，上海。
11
成都中医药大学附属医院国家传染病综合医学临床基地和传染病科，四川成都。
12
西南医科大学附属中医院，四川Lu州。
13
重庆市重庆市中医院。
14
天津市肝病研究所，天津市第二人民医院，天津。
15
加拿大不列颠哥伦比亚省温哥华市温哥华总医院消化内科，加拿大V6T1Z4。
16
墨西哥国立自治大学，墨西哥墨西哥城，Medica Sur诊所及医学基金会肝脏研究室。
17
美国加州大学欧文分校医学院胃肠病学和肝病学分部。
18岁
北方战区总医院（原沉阳军区总医院）消化内科，辽宁省沉阳市。

PMID：32437567 DOI：10.1093 / infdis / jiaa266

抽象

背景和目的：长期的核苷酸类似物（NAs）治疗可以逆转慢性乙型肝炎（CHB）中的肝纤维化，但其对纤维化消退的作用仍然有限。 ie甲-软肝（BR）在中国已被批准为抗肝纤维化中药，用于慢性肝病患者。一项多中心随机对照试验旨在评估BR对接受NAs治疗的CHB患者纤维化消退的影响。

方法：将经组织学证实为晚期纤维化或肝硬化的CHB患者随机分配接受恩替卡韦（ETV）（每天0.5mg）加BR（每天3g）或安慰剂72周。肝纤维化消退定义为Ishak纤维化分期（IFS）降低≥1分。

结果：总体上，每组有500名患者被纳入意向治疗人群。 ETV + BR组72周治疗后纤维化消退率显着更高（40％比31.8％，P = 0.0069）。在基线的388例肝硬化患者（即IFS≥5）中，ETV + BR组的肝硬化逆转率（即IFS≤4）显着更高（41.5％对30.7％，P = 0.0103）。

结论：对于目前患有晚期纤维化或肝硬化的CHB患者，在目前的NAs标准治疗中增加BR可改善肝纤维化消退。

关键字：恩替卡韦；乙型肝炎；肝硬化；肝纤维化；中药。

©2020作者。牛津大学出版社，美国传染病学会出版