Abstract: Objective To examine the variations in gut microbiota among patients infected with hepatitis B virus (HBV).Methods Stool samples were collected from 133 patients with liver disease admitted to the department of liver disease. This cohort comprised 23 HBV carriers (HBV group), 25 with hepatitis B cirrhosis (LC group), 38 with hepatocellular carcinoma (HCC group), 16 with hepatitis B-induced liver failure (ACLF group), 13 with autoimmune hepatitis (AIH group) and 18 with primary biliary cirrhosis (PBC group). Genomic DNA was isolated from these fecal samples, folloed by amplification of the V3~V4 variable region of the 16S rRNA gene using specific primers. Amplified sequences were then analyzed using UPARSE to delineate the OTUs with a set similarity threshold of ≥97%. These OTUs were annotated with taxonomic data from the Silva database. Subsequently, the QIIME software was employed to assess both the intra-and inter-group diversity of the gut microbiota.Results The predominant bacteria across the 6 groups were Firmicutes, Proteobacteria, Bacteroidota and Actinobacteria. Their combind proportions in the HBV, LC HCC, ACLF, AIH, and PBC group was 88.76%, 97.22%, 96.15%, 92.88%, 95.91% and 93.36%, respectively. Notably, the abundance of Actinobacteria was significantly greater in the HBV and HCC groups compared to the LC group. Furthermore, the abundance of Actinobacteriota, as well as other bacteria, in the HBV group surpassed that in the LC, HCC, and ACLF group. The abundance of Actinobacteriota, as well as other bacteria, was notably lower in the LCand ACLF groups compared to the PBC group. In the LC group, the presence of Bacteroidota was significantly greater than in the HCC group. While the HCC group had a higher abundance of Firmicutes compared to the HBV group. When ranking the groups by their intestinal flora anundance, the order is HBV, PBC, LC, HCC group, ACLF, and AIH.The microbial composition in the HBV, LC, HCC, and PBC groups showed significantly variances, with distinct differences in the community structures of their intestinal microflora. On the other hand, the ACLF and AIH groups displayed a more cohesive intestinal microflora community, sharing similar structural characteristics. The number of species in the HBV group was significantly higher than in the LC, HCC, and ACLF group. The LC group had fewer species than both the AIH and PBC group. Both the HCC and ACLF groups had significantly fewer species compared to the PBC group (P<0.05). As for the Shannon index, the HBV group′s score was significantly higher than the LC and ACLF groups, Additionally, the scores for the LC, HCC, and ACLF groups were all significantly lower than that of the PBC group (P<0.05).Conclusion As liver injury in HBV patients worsened, there was a noticeable decrease in the abundance and diversity of their gut microbiota. Furthermore, the abundance and diversity of gut microbiota in HBV patients were markedly different from those in AIH and PBC patients.

Key words: Hepatitis B virus, Liver injury, gut microbiota, 16sRNA