| OBJECTIVE:In order to study the differences of the chronic liver disease’s patients with hepatitis B virus in intestinal flora, and which whether could be effected by nucleoside/nucleotide analogs. It will provide a new understanding for prevention and treatment for chronic liver diseaseswith hepatitis B virus.METHODS:Fifty-eight patients, who were healthy or had chronic hepatitis B, decompensatedliver cirrhosis, or hepatic failure, were included in the study. All includings were diagnosed by using the Chinese Chronic Hepatitis B Prevention Guide in 2010 and Hepatic Failure Prevention Guide in 2012, which had not undergone therapy that could affect the intestinal microecology, such as antibiotic therapy or microecological modulators, within one month of the study. Patients were divided into the following groups:not treated with nucleoside/nucleotide analogs 20(CHB11,HF5,DLC4), treated with nucleoside/nucleotide analogs 29(CHB12,HF2,DLC15), and healthy controls 9. Stool samples were collected and intestinal microflora genomic DNA was extracted by using a fecal bacterial DNA extraction kit. The abundance and classification of intestinal flora was evaluated by using 16s rDNA amplicon sequencing analysis. Data were analyzed byusing the biology software and statistical software.RESULTS:(1)The diversity of intestinal flora in different hepatitis B related chronic liver diseases is showed that:healthy controls (3.2208±0.5797)> chronic hepatitis B group (2.6775±0.7150)> decompensated cirrhosis group (2.4137±0.6087)> liver failure group (1.9478±0.9013); the compare of intestinal flora richness in different chronic liver diseases with hepatitis B virus suggests that chronic hepatitis B group (863.40±341.19)> healthy controls (783.00±229.68)> decompensated cirrhosis group (579.30±266.42)> liver failure group (372.83±252.76).(2)The intestinal flora of different HBV related chronic liver diseases in the class level in every sample is showed the comparison and the proportion of different species are all different, but every sample is included in the Firmicutes and Bacteroidetes. Euryarchaeota is only existed in the healthy group, Fusobacterium is found in all the groups except liver failure group which are more than healthy humans. Proteobacteria in decompensated cirrhosis group is more than CHB group obviously.(3)The influence of nucleoside antiviral drugs in the intestinal flora diversity of HBV related chronic liver diseases:healthy controls (3.0)> antiviral drug treated group (2.4)> antiviral drug untreated group (2.25). (A) Bacteroides-coprocola (p=0.015), Bacteroides-plebeius (p=0.009) has the obvious difference in CHB group after antiviral treatment and compared of the healthy, three kinds of intestinal flora decreased significantly after antiviral treatment; (B) the number of Coprococcus-eutactus(p=0.04), Bacteroides-clarus (p=0.036), Eubacterium-ventriosum (p=0.028), Ruminococcus-bromii(p=0.015) the four intestinal bacterias in liver failure patients with antiviral treatment are increased than the healthy; (C) Akkermansia-muciniphila etc. three kinds of bacteria in the patients of DLC after antiviral treatment are reappeared, but lacking Bacteroides-nordii compared of the healthy. The influence of nucleoside antiviral drugs in the intestinal flora richness of HBV related chronic liver diseases:antiviral drug untreated group (3699)> antiviral drug treated group (3430)> healthy controls (1729). (A) Bacteroides-coprocola (p=0.015), Bacteroides-plebeius (p=0.009) has the obvious difference in CHB group after antiviral treatment and compared of the healthy, which are decreased significantly after antiviral treatment; (B) the number of Roseburia-inulinivorans(p=0.049) and Ruminococcus-bromii(p=0.015) in liver failure patients with antiviral treatment are increased than the healthy;(C) the intestinal flora antiviral treated group and untreated group have no obvious difference in DLC patients.(4)By comparing the composition of intestinal bacteria in treated group and untreated group, it is found that:(A) the composition of Clostridium-butyricum, Prevotella-buccae and Succinivibrio-dextrinosolvens in CHB treated group are more than CHB untreated group. But compared with the healthy, it has no difference. (B) By comparing the composition of intestinal bacteria of liver failure in treated group and untreated group, it is found that:the composition of Aeromonas-salmonicida, Alloscardovia-omnicolens, Clostridium-bartlettii, Eubacterium-ventriosum etc. fourteen intestinal bacterium in treated group are more than untreated group. Coprococcus-eutactus(p=0.040), Bacteroides-clarus(p=0.036),Eubacterium-ventriosum(p=0.028),Ruminococcus-bromii(p=0.015) four intestinal bacteria in treated group are more than the healthy group. (C) Akkermansia-muciniphila, Bacteroides-clarus and Sutterella-parvirubra are appeared in treated group of DLC, but Alloscardovia-omnicolens,Bacteroides-graminisolvens,Bacteroides-nordii,Mega sphaera-elsdenii, Methanobrevibacter-smithiiandCetobacterium-somerae six intestinal bacterias are missing. Compared of the healthy, Bacteroides-nordii(p=0.018) in treated group of DLC are missing.CONCLUSIONS:(1)Chronic hepatitis B, liver failure and decompensatedliver cirrhosis of HBV related to chronic liver disease has a unique intestinal floraand they are also related to disease type and nucleoside/nucleotide analogs.(2)Different HBV related chronic liver diseasesare obviously different of intestinal flora diversity and richness.With the progress of the disease, the kinds of intestinal flora are decreased gradually, which are most in CHB and least in hepatic failure;Different intestinal flora abundance of HBV related chronic liver disease patients are separately different, but it have a certain correlation with disease severity. Intestinal flora of patients in CHB is more than liver failure.(3)The intestinal flora ofdifferent HBV related chronic liver diseases in the class level in every sample is showed the comparison and the proportion of different species are all different, but every sample is included in theFirmicutes and Bacteroidetes.Euryarchaeotais only existed in healthy group, Fusobacteriumis found in all the groups except liver failure group which are more than healthy humans.Proteobacteria in decompensatedliver cirrhosis group is more than CHB group obviously.(4)The influences of nucleoside antiviral drugs in intestinal flora diversity and richness with HBV related chronic liver diseases are different. The influences of nucleoside antiviral drugs in intestinal flora diversity and richness with HBV related chronic liver diseases are different. The intestinal flora of missing in CHB treated group, compared with the healthy, it has no difference. The intestinal flora of missing in CHB treated group, compared with the healthy, it has partly increased and partly no difference. The intestinal flora of missing in LC treated group, compared with the healthy, it has some missing... |
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