中草藥聯合恩替卡韋可降低HBeAg陽性慢性乙型肝炎患者的非治

StephenW

Chinese herbal medicine combined with entecavir to reduce the off-therapy recurrence risk in HBeAg-positive chronic hepatitis B patients: a multicener, double-blind, randomized controlled trial in China
Xiaoke Li  1 , Ludan Zhang  1 , Mei Qiu  2 , Yi Huang  3 , Huanming Xiao  4 , Bingjiu Lu  5 , Yuyong Jiang  6 , Fuli Long  7 , Hui Lin  8 , Jinyu He  9 , Qikai Wu  10 , Mingxiang Zhang  11 , Li Wang  12 , Xiaoning Zhu  13 , Man Gong  14 , Xuehua Sun  15 , Jianguang Sun  16 , Fengxia Sun  17 , Wei Lu  18 , Weihua Xu  19 , Guang Chen  1 , Zhiguo Li  1 , Danan Gan  1 , Xianzhao Yang  1 , Hongbo Du  20 , Yong'an Ye  21
Affiliations
Affiliations

    1
    Institute of Liver Diseases, Beijing University of Chinese Medicine, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China.
    2
    Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, Guangdong Province, China.
    3
    Department of Hepatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China.
    4
    Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, 510006, China.
    5
    Department of Hepatology, Liaoning Hospital of Traditional Chinese Medicine, Shenyang, 110032, China.
    6
    Department of Hepatology, Beijing Ditan Hospital, Beijing, 100015, China.
    7
    Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, China.
    8
    Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
    9
    Department of Hepatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, 710003, China.
    10
    Department of Hepatology, The Third People's Hospital of Shenzhen, Shenzhen, 518112, Guangdong Province, China.
    11
    Department of Hepatology, The Sixth People's Hospital of Shenyang, Shenyang, 110006, China.
    12
    Department of Hepatology, Public Health Clinical Center of Chengdu, Chengdu, 610066, China.
    13
    Department of Hepatology, Affiliated traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646699, China.
    14
    Department of Hepatology, 302 Military Hospital of China, Beijing, 100039, China.
    15
    Department of Hepatology, Shanghai Shuguang Hospital, Shanghai, 200021, China.
    16
    Department of Hepatology, Shandong Hospital of Traditional Chinese Medicine, Jinan, 250011, China.
    17
    Department of Hepatology, Beijing Chinese Medicine Hospital, Beijing, 100010, China.
    18
    Department of Hepatology, The Second People's Hospital of Tianjin, Tianjin, 300000, China.
    19
    Department of Gastroenterology, The Second Hospital of Shandong University, Jinan, 250100, China.
    20
    Institute of Liver Diseases, Beijing University of Chinese Medicine, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China. [email protected].
    21
    Institute of Liver Diseases, Beijing University of Chinese Medicine, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China. [email protected].

    PMID: 32787905 DOI: 10.1186/s13063-020-04417-9

Abstract

Background: Nucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal.

Methods/design: The study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5 mg per day for consolidation therapy for 96 weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5 mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial.

Conclusion: This study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population.

Trial registration: Chinese Clinical Trial Registry No. ChiCTR1900021232 . Registered on February 2, 2019.

Keywords: Chinese herbal medicine formula; Chronic hepatitis B; Protocol; Randomized-controlled trial.

StephenW

中草藥聯合恩替卡韋可降低HBeAg陽性慢性乙型肝炎患者的非治療復發風險：一項在中國進行的多中心，雙盲，隨機對照試驗
李小可1，張六丹1，梅秋2，黃奕3，歡明肖4，炳九路5，姜育勇6，傅立隆7，惠林8，何金玉9，吳啟凱10，張明祥11，王力12，朱小寧13，曼宮14，孫雪華15，孫建光16，孫鳳霞17，魯路18，徐偉華19，光臣1，李志國1，甘丹南1，楊先兆1，洪博都20，永安野21
隸屬關係
隸屬關係

    1個
    北京中醫藥大學肝病研究所，北京中醫藥大學附屬東直門醫院，北京100700
    2
    深圳市中醫藥醫院肝病科，廣東深圳518033
    3
    重慶市中醫院醫院肝科，重慶400021
    4
    廣東省中醫院，廣東廣州510006
    5
    遼寧中醫院，遼寧沉陽110032
    6
    北京地壇醫院肝科，北京100015
    7
    廣西中醫藥大學附屬第一醫院肝科，南寧530023
    8
    福建醫科大學蒙潮肝膽醫院肝科，福州350025
    9
    陝西省中醫院肝科，陝西西安710003
    10
    深圳市第三人民醫院肝科，廣東深圳518112
    11
    沉陽市第六人民醫院肝科，遼寧沉陽110006。
    12
    成都公共衛生臨床中心肝病科，成都610066
    13
    西南醫科大學附屬中醫院肝病科，河南Lu州646699
    14
    中國人民解放軍302醫院肝科，北京100039。
    15
    上海曙光醫院肝科，上海200021
    16
    山東省中醫院肝病科，濟南250011
    17
    北京中醫院肝病科，北京100010
    18歲
    天津市第二人民醫院肝科，天津300000
    19
    山東大學第二醫院消化內科，濟南250100
    20
    北京中醫藥大學肝病研究所，北京中醫藥大學附屬東直門醫院，北京100700 [email protected]。
    21
    北京中醫藥大學肝病研究所，北京中醫藥大學附屬東直門醫院，北京100700 [email protected]。

    PMID：32787905 DOI：10.1186 / s13063-020-04417-9

抽象

背景：核苷（核苷酸）類似物（NAs）是抗慢性乙型肝炎（CHB）的一線選擇。 NAs可以有效地抑制病毒複製，HBsAg血清清除的機會很小，停藥後病毒學復發的風險很高。 NAs和中藥（TCM）的聯合治療已被廣泛接受，並已在中國被認為是一種前瞻性替代方法。根據初步工作，本研究旨在觀察中藥加恩替卡韋（ETV）對HBeAg陽性慢性乙型肝炎在降低NA停藥後復發風險方面的治療效果。

方法/設計：該研究是一項全國性，多中心，雙盲，隨機，安慰劑對照試驗，為期120週。共有18所醫院和490名合格的中國HBeAg陽性CHB患者入組，並按1：1比例隨機分配到實驗組和對照組。實驗組的患者將開具中藥配方（調肝-補虛-解毒沖劑）加ETV 0.5 mg /天，進行鞏固治療96週。對照組的患者將在同一療程中每天服用中藥顆粒安慰劑加ETV 0.5毫克。鞏固治療後，所有患者將停止使用試驗藥物，並在接下來的24週內接受嚴格監控。一旦發生臨床復發（CR），將重新開始ETV治療。主要結果是該試驗結束時的CR累積率。

結論：本研究是首次觀察到在CHB人群中進行統一的整合鞏固治療後，在NA撤出後減少復發方面的治療效果。

StephenW

https://trialsjournal.biomedcent ... /s13063-020-04417-9