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Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue (调肝健脾和血) and Tiaogan Jiedu Huashi (调肝解毒化湿) fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.

Methods

A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.

Results

The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.

Conclusion

Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

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Acknowledgement

We thank the staff from Epidemic Research Center of Peking University Third Hospital, who conducted the statistical analysis. The online therapeutic data organization system was hosted by Jiangsu Provincial Hospital.

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Authors and Affiliations

  1. Department of Gastroenterology, Institute of Liver Disease, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China

    Xiao-ke Li, Meng-yang Liu, Ke-ke Zhang, Xian-zhao Yang, Da-nan Gan, Ying Li, Peng Zhang, Zhi-guo Li, Shuo Li & Yong-an Ye

  2. Department of Hepatology, the Sixth People’s Hospital of Shenyang, Shenyang, 110006, China

    Ming-xiang Zhang

  3. Department of Hepatology, the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China

    Feng-zhen Shao

  4. Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China

    Da-qiao Zhou

  5. Department of Hepatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an, 710003, China

    Jing-dong Xue

  6. Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130021, China

    Tie-jun Liu

  7. Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, 510006, China

    Xiao-ling Chi

  8. Department of Hepatology, Liaoning Hospital of Traditional Chinese Medicine, Shenyang, 110032, China

    Bing-jiu Lu

  9. Department of Hepatology, Beijing Ditan Hospital, Beijing, 100015, China

    Xian-bo Wang

  10. Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China

    Qin Li

  11. Department of Hepatology, the 302 Military Hospital of PLA, Beijing, 100039, China

    Jun Li

  12. Department of Hepatology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, China

    De-wen Mao

  13. Department of Integrated Traditional Chinese Medicine and Western Medicine, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China

    Hua-sheng Yang

  14. Department of Traditional Chinese Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Hong-zhi Yang

  15. Department of Gastroenterology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China

    Wen-xia Zhao

  16. Department of Hepatology, Shandong Hospital of Traditional Chinese Medicine, Jinan, 250011, China

    Yong Li

  17. Department of Gastroenterology, Anhui Hospital of Traditional Chinese Medicine, Hefei, 230031, China

    Guo-liang Zhang

  18. Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, China

    Yi-ming Zhao

  19. Clinical Research Center, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, 210029, China

    Jian-dong Zou

Authors
  1. Xiao-ke Li
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  2. Ming-xiang Zhang
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  9. Xian-bo Wang
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  10. Qin Li
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  11. Jun Li
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  12. De-wen Mao
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  13. Hua-sheng Yang
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  14. Hong-zhi Yang
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  15. Wen-xia Zhao
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  16. Yong Li
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  19. Jian-dong Zou
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  20. Meng-yang Liu
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  21. Ke-ke Zhang
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  24. Ying Li
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  25. Peng Zhang
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  26. Zhi-guo Li
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  27. Shuo Li
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  28. Yong-an Ye
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Contributions

Ye YA was the project leader and designed the protocol. Li XK, Li Y, Zhang P, Li ZG and Li S drafted the manuscript. Liu MY, Zhang KK, Yang XZ, and Gan DN helped to organize and conduct the study at Dongzhimen Hospital. Zhang MX, Zhou DQ, Shao FZ, Xue JD, Chi XL, Liu TJ, Wang XB, Lu BJ, Li J, Li Q, Yang HS, Ma DW, Yang HZ, Zhao WX, Li Y and Zhang GL were principal investigators at their respective sub-centers. Zhao YM supervised the statistical analysis and Zou JD supervised the online data service.

Corresponding author

Correspondence to Yong-an Ye.

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All authors declare that they have no conflicts of interest. The sponsor of the study was not involved in the conduction, interpretation or preparation of the final manuscript.

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Li, Xk., Zhang, Mx., Shao, Fz. et al. Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial. Chin. J. Integr. Med. 26, 330–338 (2020). https://doi.org/10.1007/s11655-020-3250-0

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  • DOI: https://doi.org/10.1007/s11655-020-3250-0

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