Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial
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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.
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.
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.
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).
KeywordsAdefovir dipivoxil Tiaogan Jianpi Hexue Tiaogan Jiedu Huashi Chinese medicine HBeAg combination therapy
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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.
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.
- 4.Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. 2007;45:307–313.Google Scholar
- 14.Xia Y, Luo H, Liu JP, Gluud C. Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection. Cochrane Database Syst Rev 2013:CD009004.Google Scholar
- 18.Ye YA, Tian DL, Jiang J, Li J, Chen JJ, Li ZH, et al. Effect of Shuanghu Qinggan Granule and Yigan Yiqi Jieyu Granule plus lamivudine on chronic hepatitis B patients: a randomized double-blind placebo-controlled trial. Chin J Integr Med 2016 [Epub ahead of print].Google Scholar
- 19.Chinese Society of Hepatology and Chinese Society of Infectious Disease CMA. The guideline of prevention and treatment for chronic hepatitis B. Chin J Hepatol (Chin) 2005;13:881–891.Google Scholar
- 20.Hepatology Association of WFCMS. The TCM syndrome diagnostic criteria for Chronic hepatitis B (ALT 2× ULN). J Tradit Chin Med (Chin) 2015;56:89–90.Google Scholar
- 24.Chen WL, Luo M, Chen XP, Huang J, Chen R. The same disease with different syndromes: a proteomic study of chronic hepatitis B. J South Med Univ (Chin) 2016;36:410–413.Google Scholar