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Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial

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Abstract

Objective

To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.

Methods

This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3–V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.

Results

Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks’ treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.

Conclusion

BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

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Authors and Affiliations

  1. Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China

    Xin Chi,  Dan-ying Cheng, Xiu Sun & Hui-chun Xing

  2. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China

    Xin Chi, Xiu Sun & Shun-ai Liu

  3. National Center for Infectious Diseases, Beijing, 100015, China

    Xin Chi,  Dan-ying Cheng, Xiu Sun, Shun-ai Liu, Rong-bing Wang & Hui-chun Xing

  4. Peking University Ditan Teaching Hospital, Beijing, 100015, China

    Dan-ying Cheng & Hui-chun Xing

  5. Central of Integrated Chinese and Western Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China

    Rong-bing Wang

  6. China Traditional Chinese Medicine Holdings Co. Limited, Guangzhou, 528303, China

    Qin Chen

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  1. Xin Chi
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  2. Dan-ying Cheng
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  3. Xiu Sun
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  7. Hui-chun Xing
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Contributions

Cheng DY and Chi X were responsible for designing the study and acquisiting the data. Chi X, Sun X and Liu SA analyzed and interpreted the data. Chi X drafted the manuscript. Xing HC, Wang RB and Cheng DY critically revised the manuscript for important intellectual content. Chen Q, Sun X and Liu SA provided administrative, technical material support and study supervision. All authors approved the final version of the manuscript for publication and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Dan-ying Cheng.

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Chen Q is a staff of China Traditional Chinese Medicine Holding Co., Ltd. The authors declare that China Traditional Chinese

Additional information

Supported by the National Key Research and Development Program of China (No. 2021YFC2301800), The Capital’s Funds for Health Improvement and Research (No. CFH2018-2-2173 and CFH2020-1-2171), Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXT26)

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Appendix 1 Correlation between Intestinal Microbiota and Fibrosis Score in Patients with Hepatitis B Cirrhosis/Liver Fibrosis

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Chi, X., Cheng, Dy., Sun, X. et al. Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial. Chin. J. Integr. Med. 29, 771–781 (2023). https://doi.org/10.1007/s11655-023-3542-2

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