Background Serum HBsAg decline is an index for the effectiveness of antiviral treatment hepatitis B virus (HBV) e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. Unfortunately, for entecavir (ETV), HBsAg decline or clearance only occurs in a minority of patients even after decades of antiviral therapy. Our previous study showed that Faecal microbiota transplantation (FMT) was able to induce HBeAg clearance in patients with positive HBeAg after long-term antiviral therapy. However, the effect of FMT on HBeAg negative CHB patients after long-term antiviral therapy is still unclear. Thus, we reported a case-controlled, open-label pilot trial of FMT for HBeAg negative CHB patients.

Methods We recruited 10 patients who remained HBsAg positive following >1 years of ongoing ETV antiviral therapy. 5 of them were enrolled in the FMT arm while other 5 were enrolled in the control arm. All patients went on their previous antiviral therapy. We performed FMT via nasojejunal tube for the FMT arm every 2 weeks. The faecal microbial community was analysed using Illumina Hisequencing of 16S rDNA and bioinformatics methods. Serum HBsAg and endotoxin levels were monitored every 2 weeks.

Results Serum HBsAg declined gradually after each time of FMT in the FMT arm compared to control arm. FMT induced serum HBsAg decline up to 55.27%±8.52% in the trial group accompanied with serum endotoxin decline while serum HBsAg in the control group increased 38.07% which may closely be related to drug resistance. 16S rDNA analysis of the stools showed that gut microbiota in the FMT group transformed towards the donors. In particular, the proportion of Bifidobacterium, Streptococcus, Clostridium, Clostridiaceae, Blautia, Coprococcus and Megamonas in the gut microbiota of the FMT group decreased significantly towards the donors while the proportion of Bacteroides, Butyricimonas, Odoribacter, Prevotella, Parabacteroides, Anaerostipes, Oscillospira, Ruminococcaceae and Sutterella increased towards the donors.

Conclusions This study suggested that HBsAg decline in the serum of HBeAg negative CHB patients were detected after several times of FMT accompanied with serum endotoxin decline and the gut microbiota prone to the donors. Gut microbiota may be a new target for the treatment of HBeAg negative CHB.