Bushenjianpi formula combined with entecavir for HBeAgnegative chronic hepatitis B patients: A multicenter, randomised, double-blind, placebo-controlled trial  期刊论文  

Background: The treatment combination of traditional Chinese medicine with Western medicine results in significant decrease of serum hepatitis B virus (HBV) DNA and increase of HBeAg loss in patients with HBeAg-positive chronic hepatitis B (CHB) without any serious adverse events. We aimed to assess whether the Bushenjianpi Formula combined with entecavir could increase the HBsAg loss rate in patients with HBeAg-negative CHB. Methods: In this multicentre, randomised, double-blind, placebocontrolled trial, we recruited patients with HBeAg-negative CHB from ten third-level grade-A hospitals. The inclusion criteria included a history of HBV or HBsAg positive for more than 6 months; persistent HBeAg-negativity or HBeAb positivity; HBV DNA concentration of 1 × 104 copies per mL or higher by PCR assay at least 4 weeks before screening; alanine aminotransferase (ALT) concentrations of 2× ULN or greater, or 1 × ULN B ALT<2× ULN and Knodell histology activity index of 4 points or greater at least 4 weeks before screening; no treatment with any nucleoside analogues or interferon at least 12 months before screening; and age 18-65 years. By using a block randomisation method, patients were randomly assigned (1:1) to receive Bushenjianpi Formula combined with entecavir (treatment group) or placebo combined with entecavir (control group) for 96 weeks. All patients were treated with entecavir 0.5 mg daily and the Bushenjianpi Formula or placebo (4.5 g twice daily, oral administration). The primary outcomes is the of rate of HBsAg negative conversion and the secondary outcomes were the decline range of HBsAg and cccDNA. This study was approved by Ethical Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. All patients were written informed consent. Result: Between 2012-12-01and 2016-03-31, 620 patients with HBeAg-negative CHB were recruited, and they were were randomly assigned to the treatment group (320 patients)and the control group (320patients). After 96 weeks of treatment, the percentage of patients who had reduction in serum HBsAg ceoncentrations decreased more than 1Log10 in the treatment group (11.76%), which was significantly higher than that in control group (6.41%) (P = 0.043). The rate of HBsAg negative conversion was determined by the ratio between the number of patients whose HBsAg level was lower than 0.1 IU/ml and the total number of paitents in every group after treatment. The rate of HBsAg negative conversion was significantly greater in the treatment group (5.13%) than in control group (2.10%) (P = 0.046). The cccDNA level of liver tissue after treatment was lower than that before treatment in both groups (P = 0.001). Conclusion: The combination of Bushenjianpi Formula with entecavir could result in a decrease of serum HBsAg and liver tissue cccDNA, as well as increase of HBsAg negative conversion for patients with HBeAg-negative CHB.