Randomized Clinical Trial
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World J Gastroenterol. Dec 28, 2014; 20(48): 18458-18465
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18458
Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure
Han-Min Li, Zhi-Hua Ye, Jun Zhang, Xiang Gao, Yan-Ming Chen, Xin Yao, Jian-Xun Gu, Lei Zhan, Yang Ji, Jian-Liang Xu, Ying-He Zeng, Fan Yang, Lin Xiao, Guo-Guang Sheng, Wei Xin, Qi Long, Qing-Jing Zhu, Zhao-Hong Shi, Lian-Guo Ruan, Jia-Yao Yang, Chang-Chun Li, Hong-Bin Wu, Sheng-Duo Chen, Xin-La Luo
Han-Min Li, Xiang Gao, Xin Yao, Jian-Xun Gu, Lei Zhan, Yang Ji, Jian-Liang Xu, Ying-He Zeng, Fan Yang, Lin Xiao, Guo-Guang Sheng, Wei Xin, Qi Long, Qing-Jing Zhu, Zhao-Hong Shi, Lian-Guo Ruan, Jia-Yao Yang, Chang-Chun Li, Hong-Bin Wu, Sheng-Duo Chen, Xin-La Luo, Hepatopathy Institute, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China
Zhi-Hua Ye, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
Jun Zhang, Jingzhou Hospital of Traditional Chinese Medicine, Jinzhou 434000, Hubei Province, China
Yan-Ming Chen, Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
Author contributions: Li HM and Ye ZH contributed equally to this work; Li HM designed the research; Yao X, Gu JX, Zhan L, Ji Y, Xu JL, Zeng YH, Yang F, Xiao L, Sheng GG, Xin W, Long Q, Zhu QJ, Shi ZH, Ruan LG, Yang JY, Li CC, Wu HB, Chen SD and Luo XL performed the research; Chen YM was responsible for the identification of Chinese medicine and supervision of drugs; Ye ZH, Zhang J and Gao X analyzed the data; Li HM and Ye ZH wrote the paper.
Supported by National Science and Technology Key Projects on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment”, No. 2008ZX10005-007; Research Projects of Key Disease of National Traditional Chinese Medicine (Hepatopathy) Clinical Research Center (Hubei Province), No. JDZX2012054; National Natural Science Foundation of China, No. 81373513, No. 90709041, No. 30672590, No. 30271562, No. 30371787, No. 81102531 and No. 81274147; Key Projects of Natural Science Foundation of Hubei Province, No. 2011CDB463; Specialized Research Fund for the Doctoral Programs in Institution of Higher Education, No. 20124230110001; Key Subjects of Department of Science and Technology of Wuhan City, No. 201260523199
Correspondence to: Han-Min Li, MD, PhD, Professor, Hepatopathy Institute, Affiliated Hospital of Hubei University of Chinese Medicine, Huayuan No. 4, Wuchang District, Wuhan 430061, Hubei Province, China. lihanmin69@126.com
Telephone: +86-27-88929180 Fax: +86-27-88929180
Received: April 20, 2014
Revised: July 3, 2014
Accepted: August 13, 2014
Published online: December 28, 2014
Processing time: 260 Days and 10.7 Hours
Abstract

AIM: To study the clinical efficacy of traditional Chinese medicine (TCM) intervention “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) for treating liver failure due to chronic hepatitis B.

METHODS: We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a “tonifying qi and detoxification” (“TQD”) group (72 patients); and (3) a “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the “TQD” group were given a TCM formula “tonifying qi and detoxification” and general internal medicine treatment; patients in the “TTK” group were given a TCM formula of “TTK” and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.

RESULTS: At the 48-wk post-treatment time point, the patient fatality rates in the MMC, “TQD”, and “TTK” groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups (P > 0.05). Patients in the “TTK” group had significantly higher levels of serum total bilirubin compared to MMC subjects (339.40 μmol/L ± 270.09 μmol/L vs 176.13 μmol/L ± 185.70 μmol/L, P = 0.014). Serum albumin levels were significantly increased in both the “TQD” group and “TTK” group as compared with the MMC group (31.30 g/L ± 4.77 g/L, 30.72 g/L ± 2.89 g/L vs 28.57 g/L ± 4.56 g/L, P < 0.05). There were no significant differences in levels of alanine transaminase among the three groups (P > 0.05). Safety data showed that there was one case of stomachache in the “TQD” group and one case of gastrointestinal side effect in the “TTK” group.

CONCLUSION: Treatment with “TTK” improved the survival rates of patients with liver failure due to chronic hepatitis B. Additionally, liver tissue was regenerated and liver function was restored.

Keywords: Clinical study; “Tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”); Liver regeneration; Treatment with integrated traditional and Western medicine; Chronic hepatitis B-associated liver failure

Core tip: We conducted a randomized controlled clinical trial to observe the effects of traditional Chinese medicine intervention “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) in treating liver failure due to chronic hepatitis B virus infection. The fatality rate in the group treated with “TTK” was significantly lower than those in the other two groups (16.67% vs 51.61%, 35.38%, P = 0.010). The mechanism for this effect may be related to promotion of liver regeneration and repair through affecting stem cells and their microenvironment.