Objective:

2

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:

2

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:

2

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:

2

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