Short-term effects of direct-acting antiviral agents on inflammation and gut microbiota in hepatitis C-infected patients

Liver damage is associated with gut dysbiosis. New direct-acting antiviral agents (DAAs) are able to eradicate hepatitis C virus (HCV) from the body. However, the short and medium-term effects of DAAs at gut level before advanced liver damage occurs have not been evaluated yet. Thus, we investigated the impact of HCV and DAAs on gut microbiota composition (GM) and systemic inflammation. To achieve this objective, twenty-three non HCV-infected controls and 22 HCV-infected patients were recruited. Only non-cirrhotic patients (fibrosis stage 0-3) were included to avoid the direct impact of cirrhosis and portal hypertension on gut. The HCV-groups were evaluated before the treatment, after completing DAAs treatment and after 3 months. Fecal bacterial 16S rDNA was ultrasequenced and several biochemical/metabolic/inflammatory parameters were quantified. HCV infection was accompanied by a significant increase in TNF alpha plasma levels. DAAs were able to reduce this increase, especially in lower fibrosis grades. HCV infection was not accompanied by dramatic changes in alpha-diversity and was not recovered after HCV negativization, although a complete restoration was observed in lower fibrosis degrees. Six phyla, 15 genera and 9 bacterial species resulted differentially abundant among the groups. These differences were almost blunted with lower fibrosis. In summary, neither the usage of DAAs nor 3 months in sustained viral response were able to counteract the changes induced by HCV at gut level. The partial restoration observed in inflammation and alpha-diversity was only observed in low fibrosis degrees. Thus, it is urgent to begin treatment with DAAs as soon as possible.