It is well accepted that liver diseases and their outcomes are associated with intestinal microbiota but causality is difficult to establish. The intestinal microbiota is altered in patients with hepatitis C. As chronic HCV infection can now be cured in almost all patients, it is an ideal model to study the influence of liver disease on the microbiota. We aimed to analyze prospectively the changes in the gut microbiome in patients who received direct acting antivirals (DAA) and achieved sustained virological response (SVR). Amplicon sequencing of the V1-V2 region in the 16S rRNA gene was performed in stool samples of patients with chronic hepatitis C. Patients in the treatment group received direct acting antivirals (n=65) whereas in the control group no DAA were given (n=33). Only patients achieving SVR were included. The alpha diversity increased numerical but not significantly from baseline to SVR24/48 (2.784±0.248 vs. 2.846±0.224; p= 0.057). When stratifying for the presence of liver cirrhosis, a significant increase in diversity was only seen in patients without cirrhosis. Differences in the microbial community structure induced by the achievement of SVR were only observed in patients without liver cirrhosis. In patients with liver cirrhosis and in the control group, no significant differences were observed. In conclusion, the achievement of SVR24/48 in patients with chronic HCV was associated with changes in the intestinal microbiota. However, these changes were only seen in patients without liver cirrhosis. A major role of liver remodeling on the intestinal microbiota is indicated by the dynamics of the intestinal microbial community structure depending on the stage of fibrosis in patients resolving chronic hepatitis C
