恩替卡韦联合别甲软肝复方降低中国慢性乙型肝炎患者肝癌

StephenW

恩替卡韦联合别甲软肝复方降低中国慢性乙型肝炎患者肝癌风险
董骥 1 , 严辰 1 , 景峰碧 2 , 清华尚 3 , 刘华宝 4 , 王家波 5 , 林潭 6 , 王靖 7 , 陈永平 8 , 秦立 9 , 清华龙 10 , 莱城宋 11 ,李江 12 , 光明 肖 13 , 于祖江 14 , 梁晨 15 , 王晓东 8 , 大陈 9 , 李志勤 14 , 郑东 1 , 杨永平 16
    1
    中国人民解放军总医院第五医学中心肝病科，北京，中国
    2
    中国人民解放军总医院第五医学中心感染科主任医师，北京，中国
    3
    中国人民解放军联勤保​​障部队第960医院肝病诊疗中心，山东泰安
    4
    【作者单位】： 重庆市中医院;
    5
    中国人民解放军总医院第五医学中心肝病高级科，北京，中国；首都医科大学中医学院，北京，中国。
    6
    【作者单位】： 安徽省阜阳市第二人民医院肝病科;
    7
    【作者单位】： 西南医科大学附属中医院;四川省泸州市;
    8
    【作者单位】： 温州医科大学第一附属医院感染与肝病科;
    9
    【作者单位】： 福建省福州市福州传染病医院;
    10
    【作者单位】： 江西省宜春市宜春市人民医院感染与肝病科;
    11
    【作者单位】： 安徽省太和市太和中医院;
    12
    【作者单位】： 第三军医大学第一附属医院(西南医院)感染科;
    13
    广州市第八人民医院，中国广东省广州市。
    14
    【作者单位】： 郑州大学第一附属医院感染科;
    15
    上海市公共卫生临床中心肝病科。
    16
    中国人民解放军总医院第五医学中心肝病科，北京，中国电子地址：[email protected]。

    PMID：35985545 DOI：10.1016/j.jhep.2022.07.018

抽象的

背景与目的：慢性乙型肝炎（CHB）和肝纤维化是肝细胞癌（HCC）的高危因素。我们评估了 ETV 加鳖甲软肝复方 (BRC)，一种抗纤维化的中药，是否可以进一步降低 Ishak 纤维化评分≥3 分的初治中国慢性乙型肝炎患者的 HCC 风险，该患者来自我们的父母双盲随机安慰剂对照试验。

方法：在对 ETV+BRC 和 ETV+安慰剂治疗进行 72 周比较后，参与者有资格进入开放标签治疗阶段，每 6 个月进行一次随访。主要[次要]终点是HCC的发生率[肝脏相关死亡、非HCC事件和非肝脏相关死亡]。为事件发生时间分析定义了改良的意向治疗 (mITT)、意向治疗 (ITT) 和符合方案 (PP) 人群。

结果：共招募患者1000例，中位年龄42.0岁，男性占69.9%，HBeAg阳性占58.3%。在 mITT 人群中，ETV+BRC 的 HCC [肝脏相关死亡] 7 年累积发病率为 4.7% [0.2%]，显着低于 ETV 的 9.3% [2.2%] (p =0.008 [p =0.030]）。值得注意的是，与 ETV 治疗相比，ETV+BRC 治疗在第 72 周未达到纤维化消退的患者的 HCC 发生率较低（p = 0.018）。两组之间的其他两个次要终点或安全性概况没有差异。包括治疗分配作为参数的多变量 Cox 比例回归分析也表明 ETV+BRC 治疗是 HCC 发病率的保护因素。 ITT 和 PP 分析显示一致的结果。

结论：ETV联合BRC联合治疗可进一步降低CHB晚期纤维化或肝硬化患者发生HCC和肝脏相关死亡的风险，这可能对HCC的预防具有重要的临床意义。总结 ●在恩替卡韦 (ETV) 治疗无法消除乙型肝炎病毒的情况下，确定如何进一步降低肝细胞癌 (HCC) 的风险在临床上很重要。 ●我们对我们72周的父母前瞻性随机安慰剂对照试验进行了长期扩展，结果表明，抗纤维化中药（TCM）鳖甲软肝复方（BRC）可以进一步降低在接受 ETV 治疗的中国 CHB 患者中，HCC 增加 51.1%，肝脏相关死亡减少 89.9%。●鉴于HCC预后不良，该研究结果可能具有重要的临床意义，可作为进一步研究中医机制的基础，以探索更有效的降低HCC风险的策略。

关键词：乙型肝炎病毒； 肝活检； 肝脏硬度测量； 长期结果； 核苷酸类似物； 中药。

版权所有 © 2022 作者。 由 Elsevier B.V. 出版。保留所有权利。

StephenW

Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B
Dong Ji  1 , Yan Chen  1 , Jingfeng Bi  2 , Qinghua Shang  3 , Huabao Liu  4 , Jia-Bo Wang  5 , Lin Tan  6 , Jing Wang  7 , Yongping Chen  8 , Qin Li  9 , Qinghua Long  10 , Laicheng Song  11 , Li Jiang  12 , Guangming Xiao  13 , Zujiang Yu  14 , Liang Chen  15 , Xiaodong Wang  8 , Da Chen  9 , Zhiqin Li  14 , Zheng Dong  1 , Yongping Yang  16
    1
    Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
    2
    Senior Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
    3
    Diagnosis and Treatment Center for Liver Diseases, The 960th Hospital of Chinese PLA Joint Logistics Support Force, Tai'an, Shandong, China.
    4
    Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China.
    5
    Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
    6
    Liver Disease Department, The Second People's Hospital of Fuyang City, Fuyang, Anhui, China.
    7
    Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China.
    8
    Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
    9
    Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian, China.
    10
    Department of Infection and Liver Disease, Yichun People's Hospital, Yichun, Jiangxi, China.
    11
    Traditional Chinese Medicine Hospital of Taihe, Taihe, Anhui, China.
    12
    Department of Infectious Diseases, The First Affiliated Hospital (the Southwest Hospital) of the Third Military Medical University, Chongqing, China.
    13
    Guangzhou 8th People's Hospital, Guangzhou, Guangdong, China.
    14
    Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
    15
    Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China.
    16
    Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: [email protected].

    PMID: 35985545 DOI: 10.1016/j.jhep.2022.07.018

Abstract

Background & aims: Chronic hepatitis B (CHB) and liver fibrosis are high-risk factors for hepatocellular carcinoma (HCC). We assessed whether ETV plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese CHB patients with Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial.

Methods: After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis.

Results: A total of 1000 patients were recruited, the median age was 42.0 years, 69.9% were male, 58.3% had positive HBeAg. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV (p =0.008 [p =0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than did ETV treatment (p =0.018). There were no differences in the other two secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis including the treatment allocation as a parameter also demonstrated that ETV+BRC treatment was a protective factor for the incidence of HCC. The ITT and PP analyses showed consistent results.

Conclusions: ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in CHB patients with advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. Lay summary ●It is clinically important to determine how to further reduce the risk of hepatocellular carcinoma (HCC) when it is not possible to eliminate hepatitis B virus with entecavir (ETV) treatment. ●We performed a long-term extension of our 72-week parent prospective randomized placebo-controlled trial, which revealed that the Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine (TCM), could further reduce the incidence of HCC by 51.1% and liver-related deaths by 89.9% in Chinese CHB patients receiving ETV treatment.●Given the poor prognosis of HCC, the findings may have important clinical implications and serve as a basis for further mechanism studies of TCM to explore a more effective strategy to reduce the risk of HCC.

Keywords: Hepatitis B virus; Liver biopsy; Liver stiffness measurement; Long-term outcomes; Nucleot(s)ide analogs; Traditional Chinese medicine.

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

StephenW

http://www.journal-of-hepatology.eu/article/S0168827822029828/pdf

了凡小子

楼主辛苦！

tim889

72周的双盲，随后换成6年的open-label？为啥不一直双盲下去，而中途要换open-label？哈哈哈 我内心又邪恶了