Entecavir combining Chinese herbal medicine for HBeAg-positive chronic hepatitis B patients: a randomized, controlled trial
Xiaoke Li 1 , Daqiao Zhou 2 , Xiaoling Chi 3 , Qin Li 4 , Li Wang 5 , Bingjiu Lu 6 , Dewen Mao 7 , Qikai Wu 8 , Xianbo Wang 9 , Mingxiang Zhang 10 , Jingdong Xue 11 , Yong Li 12 , Wei Lu 13 , Jianchun Guo 14 , Feng Jiang 1 , Xinwei Zhang 15 , Zhiguo Li 1 , Xianzhao Yang 1 , Hui Guo 16 , Danan Gan 1 , Liyun He 17 , Lin Luo 17 , Ludan Zhang 1 , Hongbo Du 18 , Yong'an Ye 19
Affiliations
Affiliations
1
Department of Gastroenterology, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (BUCM), Institute of Liver Diseases, BUCM, No. 5 Haiyuncang road, Dongcheng District, Beijing, 100700, China.
2
Department of Hepatology, Shenzhen TCM Hospital, No. 1 Fuhua Road, Futian District, Shenzhen, 518033, China.
3
Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Dade Road 111, Guangzhou, 510120, Guangdong, China.
4
Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, No. 312 Xihong road, Gulou District, Fujian, 350025, Fuzhou, China.
5
Department of Hepatology, Public Health Clinical Center of Chengdu, No. 377 Jingming Road, Jinjiang District, Chengdu, 610066, Sichuan, China.
6
Department of Hepatology, Liaoning Hospital of TCM, Huanggu District, No. 33, Beiling Street, Shenyang, 110032, Liaoning, China.
7
Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89-9, Dongge road, Nanning, 530023, Guangxi, China.
8
Department of Hepatology, The Third People's Hospital of Shenzhen, No. 29 Bujibulan Road, Longgang District, Shenzhen, 518112, China.
9
Department of Hepatology, Beijing Ditan Hospital, No. 8 Jingshun East Road, Chaoyang District, Beijing, 100015, China.
10
Department of Hepatology, The Sixth People's Hospital of Shenyang, No. 85 Heping south road, Heping District, Shenyang, 110006, Liaoning, China.
11
Department of Hepatology, Shaanxi Hospital of TCM, No. 4 Xihuamen, Lianhu District, Xi'an, 710003, Shaanxi, China.
12
Department of Hepatology, The Affiliated Hospital of Shandong University of TCM, No. 42 Wenhua West Road, Jinan, 250011, Shandong, China.
13
Department of Hepatology, Tianjin Second People's Hospital, No.7 Sudi South Road, Nankai District, Tianjin, 300192, China.
14
Department of Hepatology, Xixi Hospital of Hangzhou, No. 2 Hengbu road, Liuxiazhen, Xihu District, Hangzhou, 310023, Zhejiang, China.
15
Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, No.100 West Fourth Ring Road, Beijing, 100039, China.
16
Department of Hepatology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 314 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
17
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medicine Sciences, No. 16, Dongzhimen South Street, Dongcheng District, Beijing, 100700, China.
18
Department of Gastroenterology, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (BUCM), Institute of Liver Diseases, BUCM, No. 5 Haiyuncang road, Dongcheng District, Beijing, 100700, China. [email protected].
19
Department of Gastroenterology, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (BUCM), Institute of Liver Diseases, BUCM, No. 5 Haiyuncang road, Dongcheng District, Beijing, 100700, China. [email protected].
PMID: 33128206 DOI: 10.1007/s12072-020-10097-z
Abstract
Background and aim: Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients.
Methods: 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108.
Results: The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week.
Conclusion: Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile.
背景与目的:中药(TCM)和核苷类似物(NAs)在中国已被广泛接受和开处方。在这项双盲,安慰剂对照,随机,多中心试验中,我们评估了恩替卡韦(ETV)加上调肝益皮颗粒(TGYP)和调肝健肌Pi Du Du颗粒(TGJPJD)可以增加中国患者乙型肝炎e抗原(HBeAg)丢失率。
方法:在这项为期108周的试验中,将596名符合条件的参与者以1:1的比例随机分配到两个研究组:实验组被分配了ETV加中药配方。对照组被分配ETV加中药安慰剂。我们比较了第108周结束时两组之间的HBeAg丢失率作为主要结局。次要结果包括第108周时的乙型肝炎表面抗原(HBsAg)水平,无法检测到的HBV-DNA比例和肝酶(ALT,AST,GGT)。