Disorder Of Gut Microbiome With Chronic Liver Diseases And Improvement Effect Of Probiotics Intervention On Serum Markers Of Liver Fibrosis

ObjectiveTo comparatively analysis of characteristics of gut dominant microbiota in patients with chronic hepatitis B,hepatitis B cirrhosis and autoimmune liver disease,and the changes and correlation of gut dominant microbiota and serum markers of liver fibrosis after Interfering with Probiotics.MethodsThis study collected 104 patients and 30 healthy controls from the outpatient department of Zhejiang University International Hospital between January 2016 and January 2018.According to the clinical diagnosis,the patients were divided into chronic hepatitis B group(47 cases),hepatitis B cirrhosis group(38 cases)and autoimmune liver disease group(19 cases,including PBC and AIH).Analyze the laboratory indicators,the structural features and differences of gut dominant microbiota and their correlation with serum markers of liver fibrosis in the three groups of patients.Have an intervention on 9 chronic hepatitis B patients and 11 hepatitis B cirrhosis patients with probiotics,and observe and analyze the changes of gut dominant microbiota and serum markers of liver fibrosis before and after intervention in both groups and their correlation.ResultsIn the three case groups(chronic hepatitis B group,hepatitis B cirrhosis group,and autoimmune liver disease group),middle-aged men were the majority(the overall average age was 44.144±9.92 years,and 69.2%males),but the majority of autoimmune liver disease were women(84.2%).There was a statistically significant difference in the age and sex of the three groups of patients(P<0.001).Among the three groups,there were very significant differences statistically(P<0.001)existing in RBC,PLT,GLB,A/G,AKP and ADA,and significant differences statistically(P<0.05)existing in HB,ALB,GGT,CHE,TBA,EPI-Cr and HDL.Among them,the changes of RBC,GLB,A/G,AKP,ADA,HB,ALB,GGT,CHE,TBA,EPI-Cr and HDL were the greatest in autoimmune liver disease group,and PLT decreased most obviously in the hepatitis B cirrhosis group.A comparative analysis of the case groups and the healthy controls group showed that there were very significant differences statistically in the gut dominant microbiota Bacteroides,Bifidobacterium,Clostridium butyricum,Ectomycota,Trichoderma,Enterobacteriaceae,and B/E values(P<0.001).Comparing with the healthy control group,there were statistically significant differences in the bacterial flora in 8 patients with chronic hepatitis B virus,and there were statistically significant differences in 7 bacterial populations in the hepatitis B cirrhosis patient group and autoimmunity.There were statistically significant differences in the 4 bacterial groups in the group of patients with hepatic disease.The comparison of the three groups of healthy controls,chronic hepatitis B patients,and hepatitis B cirrhosis patients showed that Enterococci,Bacteroides,Bifidobacterium,Clostridium perfringens,Clostridium butyricum,Ectomycota,Saccharomyces and Enterobacteriaceae were very significant differences(P<0.001)and Faecalibacterium prausnitzii was significant difference(P<0.05).The mean abundance of bacteria in the chronic hepatitis B group was the largest.There was a statistically significant difference in LN,HA,PIIIP,and CGIV among the case groups,with the four serum markers of liver fibrosis being highest in the autoimmune liver disease group.The correlation analysis between the gut dominant microbiota and serum markers of liver fibrosis in each case group showed that there were 3 pairs,12 pairs and 1 pair of significant correlation respectively in the chronic hepatitis B group,the hepatitis B cirrhosis group and the autoimmune liver disease group.Probiotics intervened in 9 patients with chronic hepatitis B and 11 patients with hepatitis B cirrhosis.Before and after the intervention,the serum markers of liver fibrosis of the two groups both decreased(A>0),and the gut dominant microbiota Faecalibacterium prausnitzii,Enterococci,Bacteroides,Lactobacillus,Bifidobacterium,Clostridium perenne,Clostridium butyricum,Ectomycoccus and atopobium cluster all increased in mean value(?<0),and B/E values also increased(?<0),but Enterobacteriaceae showed a downward trend(?>0).Paired t-tests within the group and Pearson or Spearman correlation coefficient analysis found that some markers were correlated.ConclusionsPatients with chronic hepatitis B,hepatitis B cirrhosis,and autoimmune liver disease have a significant disorder of gut dominant microbiota.From the state of health,chronic hepatitis B,to the evolvement state of hepatitis B liver cirrhosis,the abundance of gut dominant microbiota prevailed first and then decreased.There was a significant difference in serum markers of liver fibrosis between them and with the progression of chronic hepatitis B to cirrhosis,the relationship between gut dominant microbiota and serum markers of liver fibrosis was more closely related.After the intervention of the probiotics,the harmful bacteria decreased,while many beneficial bacteria increased.The disorder of the dominant intestinal flora was corrected,and serum markers of liver fibrosis were improved compared to the pre-intervention,moreover some gut microbiota and liver fibrosis indicators are relevant,suggesting that it was a role for the gut dominant microbiota as a potential therapeutic target for improving liver fibrosis.