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

  • Xiao-ke Li
  • Ming-xiang Zhang
  • Feng-zhen Shao
  • Da-qiao Zhou
  • Jing-dong Xue
  • Tie-jun Liu
  • Xiao-ling Chi
  • Bing-jiu Lu
  • Xian-bo Wang
  • Qin Li
  • Jun Li
  • De-wen Mao
  • Hua-sheng Yang
  • Hong-zhi Yang
  • Wen-xia Zhao
  • Yong Li
  • Guo-liang Zhang
  • Yi-ming Zhao
  • Jian-dong Zou
  • Meng-yang Liu
  • Ke-ke Zhang
  • Xian-zhao Yang
  • Da-nan Gan
  • Ying Li
  • Peng Zhang
  • Zhi-guo Li
  • Shuo Li
  • Yong-an YeEmail author
Original Article
  • 5 Downloads

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).

Keywords

Adefovir dipivoxil Tiaogan Jianpi Hexue Tiaogan Jiedu Huashi Chinese medicine HBeAg combination therapy 

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Notes

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.

Author 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.

Conflict of Interest

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.

Supplementary material

11655_2020_3250_MOESM1_ESM.pdf (111 kb)
Supplementary material, approximately 111 KB.

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Copyright information

© The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Xiao-ke Li
    • 1
  • Ming-xiang Zhang
    • 2
  • Feng-zhen Shao
    • 3
  • Da-qiao Zhou
    • 4
  • Jing-dong Xue
    • 5
  • Tie-jun Liu
    • 6
  • Xiao-ling Chi
    • 7
  • Bing-jiu Lu
    • 8
  • Xian-bo Wang
    • 9
  • Qin Li
    • 10
  • Jun Li
    • 11
  • De-wen Mao
    • 12
  • Hua-sheng Yang
    • 13
  • Hong-zhi Yang
    • 14
  • Wen-xia Zhao
    • 15
  • Yong Li
    • 16
  • Guo-liang Zhang
    • 17
  • Yi-ming Zhao
    • 18
  • Jian-dong Zou
    • 19
  • Meng-yang Liu
    • 1
  • Ke-ke Zhang
    • 1
  • Xian-zhao Yang
    • 1
  • Da-nan Gan
    • 1
  • Ying Li
    • 1
  • Peng Zhang
    • 1
  • Zhi-guo Li
    • 1
  • Shuo Li
    • 1
  • Yong-an Ye
    • 1
    Email author
  1. 1.Department of Gastroenterology, Institute of Liver DiseaseDongzhimen Hospital affiliated to Beijing University of Chinese MedicineBeijingChina
  2. 2.Department of Hepatologythe Sixth People’s Hospital of ShenyangShenyangChina
  3. 3.Department of Hepatologythe First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
  4. 4.Department of HepatologyShenzhen Traditional Chinese Medicine HospitalShenzhenChina
  5. 5.Department of HepatologyShaanxi Hospital of Traditional Chinese MedicineXi’anChina
  6. 6.Affiliated Hospital of Changchun University of Chinese MedicineChangchunChina
  7. 7.Department of HepatologyGuangdong Hospital of Traditional Chinese MedicineGuangzhouChina
  8. 8.Department of HepatologyLiaoning Hospital of Traditional Chinese MedicineShenyangChina
  9. 9.Department of HepatologyBeijing Ditan HospitalBeijingChina
  10. 10.Department of HepatologyMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouChina
  11. 11.Department of Hepatologythe 302 Military Hospital of PLABeijingChina
  12. 12.Department of Hepatologythe First Affiliated Hospital of Guangxi University of Chinese MedicineNanningChina
  13. 13.Department of Integrated Traditional Chinese Medicine and Western Medicine, Beijing YouAn HospitalCapital Medical UniversityBeijingChina
  14. 14.Department of Traditional Chinese MedicineThird Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  15. 15.Department of Gastroenterologythe First Affiliated Hospital of Henan University of Chinese MedicineZhengzhouChina
  16. 16.Department of HepatologyShandong Hospital of Traditional Chinese MedicineJinanChina
  17. 17.Department of GastroenterologyAnhui Hospital of Traditional Chinese MedicineHefeiChina
  18. 18.Research Center of Clinical EpidemiologyPeking University Third HospitalBeijingChina
  19. 19.Clinical Research CenterAffiliated Hospital of Nanjing University of Traditional Chinese MedicineNanjingChina

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