Fecal Microbiota Transplantation Induces HBeAg Clearance In Patients With Chronic Hepatitis B With Persistent Positive HBeAg

Background and Aims:Chronic hepatitis B(CHB)is a worldwide disease whereas only a small part of patients can achieve the standard of ceasing treatment even after years of oral antiviral therapy.Fecal microbiota transplantation(FMT)has been shown to induce remission in several diseases including Clostridium difficile-related colitis.In this study,we investigated the efficacy of FMT on patients with persistent positive HBeAg following a long-term course of nucleos(t)ide analogues(Nas)treatment.Methods:Eighteen patients were recruited for this open label,single-blind,intention-to-treatment study.Five patients who remained HBeAg-positive following>3 years of antiviral treatment were enrolled in this trial of FMT.These patients received FMT from healthy anonymous donors via upper endoscopy every 4 weeks.Thirteen patients did not receive the FMT and were enrolled as controls.HBeAg clearance,defined as the loss of HBeAg,was assessed for each patient.Patients provided stool samples prior to the study and one week after each FMT for microbiota analysis.Blood samples were collected before FMT and 4 weeks after FMT for HBeAg measurement.Results:One patient exited the trial after five FMT treatments due to an economic consideration.The other four patients achieved HBeAg clearance after one to seven FMT treatments.In contrast,none of the control patients achieved HBeAg clearance.There were no significant adverse events related to FMT.Compared with the baseline,stool samples from patients collected following FMT had greater microbial diversity.Conclusion:FMT may induce HBeAg clearance,which otherwise could not be achieved with long-term antiviral therapy,without significant adverse events.HBeAg-positive patients receiving indefinite oral antiviral therapy may benefit from FMT.