Abstract
The gut microbiota has an important role in the pathogenesis of hepatic encephalopathy(HE). Rifaximin, an intestinal non-absorbable antibacterial agent, is effective in the treatment of HE. However, whether long-term prophylactic use induces antibacterial resistance and its mechanism for treating HE remains unclear. This prospective study assessed the impact of 12 weeks rifaximin administration on the gut microbiota and resistome in cirrhotic patients. Fecal sampling was conducted 1 day before the first rifaximin administration and at Weeks 1, 2, 4, 6, 8, 10, 12 of the study. Thirty cirrhotic patients who were in remission from recurrent HE was enrolled to receive rifaximin (400mg TID for 12 weeks). Rifaximin improved hyperammonemia and cognitive function in the 21 patients who completed rifaximin treatment. The dynamic observations showed the gut microbiota diversity, composition and the number of resistance genes, plasmids, insertion sequences did not change significantly during the period(P>0.05). Metabolic pathways such as aromatic amino acids, tryptophan synthesis, urea cycle, and LPS synthesis reduced. No new antimicrobial resistance genes was emergenced. However, the number of aminoglycosides, rifamycin and phenolic resistance genes increased, whereas tetracycline, fosfomycin and cephamycin decreased (P<0.05). Changes in the abundance of E. coli, K. pneumoniae, and B. longum strains correlated with changes of resistance genes. Prophylactic use of rifaximin for 12 weeks improved hyperammonemia and neurophysiological function, maintained gut microbiota diversity, composition and did not change the overall resistome. Rifaximin altered expression of HE-related metabolic pathways. All of these effects could play a key role in preventing HE. Clinical Trial Registration: ChiCTR1900022234 (registered at the Chinese Clinical Trial Registry).
Highlights
Chronic liver disease is common, and hepatic encephalopathy (HE) is a common serious complication with a high mortality rate in patients with end-stage cirrhosis
Sung et al found that the diversity of the gut microbiota decreased during onset of HE, and recovered partially during the recovery period, suggesting that changes in diversity of the gut microbiota are involved in the pathogenesis of HE (Sung et al, 2019)
We found that the diversity of the gut microbiota decreased significantly in patients who developed HE compared with those who did not, and that the decrease was most pronounced during the onset of HE
Summary
Chronic liver disease is common, and hepatic encephalopathy (HE) is a common serious complication with a high mortality rate in patients with end-stage cirrhosis. The main drugs currently used for prevention and treatment of HE are Lornithine-L-aspartate, lactulose, lactitol, and rifaximin. In 2010, the US FDA approved rifaximin for prevention and treatment of HE; EASL-AASLD guidelines (2014 version) for the treatment of HE recommends this drug as an effective add-on treatment for patients with overt HE (i.e., those who develop the disease while taking lactulose) and for preventing recurrence of HE. The Consensus Opinion on the Diagnosis and Treatment of HE in China (2013) recommends rifaximin as a widely available drug for preventing the recurrence of HE (FDA Approves New Use of Xifaxan for Patients With Liver Disease, 2010); Chinese Society of Hepatology Chinese Medical Association, 2013; American Association for the Study of Liver Diseases and European Association for the Study of the Liver, 2014). The mechanism by which rifaximin prevents and treats of HE is still not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
