Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis

Background: The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis. Aim: To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis. Methods: Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1 year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period. Results: The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged. Conclusions: Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.