Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Chin J Integr Med. 2023 Sep;29(9):771-781. doi: 10.1007/s11655-023-3542-2. Epub 2023 May 24.
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).
目的：分析鳖甲煎丸对乙型肝炎肝硬化/肝纤维化患者肠道微生物群的疗效，并探讨其与肝纤维化的关系。
方法：这是一项前瞻性、随机、双盲对照临床试验。采用分层区组随机化方法，将 35 例乙型肝炎肝硬化/肝纤维化患者随机分为（1:1）恩替卡韦（0.5 mg/d）联合鳖甲煎丸（3 g/次，每日 3 次）或安慰剂（模拟剂作为对照组，模拟剂 3 g/次，每日 3 次）治疗 48 周。分别于治疗前和治疗 48 周时采集患者的血和粪便标本。检测肝功能、肾功能和血液学指标。采用 16S rDNA V3-V4 高通量测序分析粪便样本，比较两组治疗前后肠道微生物群的变化，并分析其与肝纤维化的相关性。
结果：与对照组相比，鳖甲煎丸组的肝功能、肾功能和血液学指标无显著差异，但鳖甲煎丸组的肝纤维化改善率更高（94.4%比 64.7%，P=0.041）。基于加权 UniFrac 距离的主坐标分析（PCoA）显示鳖甲煎丸治疗前后肠道微生物群落多样性有显著差异（P<0.01 和 P=0.003）。治疗 48 周后，有益菌（双歧杆菌、乳杆菌、粪肠球菌和布劳特氏菌）的丰度增加，而潜在的致病性细菌（包括大肠杆菌、拟杆菌、瘤胃球菌、副拟杆菌和普雷沃氏菌）的丰度降低，其中瘤胃球菌和副拟杆菌与肝纤维化程度呈显著正相关（r=0.34，P=0.04；r=0.38，P=0.02）。整个治疗过程中对照组的肠道微生物群没有明显变化。
结论：鳖甲煎丸对乙型肝炎肝硬化/肝纤维化患者的肠道微生物群有一定的调节作用（ChiCTR1800016801）。
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