Impact of oral antiviral therapy against HCV on gut microbiota. A prospective study

The intestinal microbiota plays a fundamental role in physiological homeostasis as well as in pathologic conditions. Hepatitis C virus is the leading cause of chronic liver diseases wordwide. The treatment of this infection has been revolutioned by the availability of direct-acting antiviral agent which guarantee high rate (about 95%) of viral clearance. Few studies have assessed the change in gut microbiota in patients treated with direct-acting antiviral agents against HCV and many aspects still need to be clarified. The aim of the study was to evaluate the effects of antiviral therapy on gut microbiota. We enrolled patients with HCV-related chronic liver disease attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from January 2017 to March 2018, treated with DAAs. For each patient, a fecal sample was collected and analyzed for the assessment of the microbial diversity before the start of therapy and by SVR12 time. We exluded patients who received antibiotics in the last 6 months. Twelve patients were enrolled (6 male, 8 genotype 1 (1 subtype 1a), 4 genotype 2). Fibrosis score were F0 in 1 patient, F2 in 1 patient, F3 in 4 patients and cirrhosis in the remaining 6 (all in Child-Pugh class A). All were treated with DAAs for 12 weeks (5 with Paritaprevir-Ombitasvir-Ritonavir-Dasabuvir, 3 with Sofosbuvir-Ledipasvir, 1 with Sofosbuvir-Ribavirin, 1 with Sofosbuvir-Daclatasvir, 1 with Sofosbuvir-Velpatasvir) and 100% achieved SVR12. In all patients, we observed a trend in reduction of potentially pathogenic microorganisms (i.e. Enterobacteriaceae). Furthermore, a trend of increase in α-diversity was observed in patients by SVR12 compared to baseline. This trend was markedly more evident in patients without liver cirrhosis than in those with cirrhosis. Our study shows that viral eradication obtained with DAA is associated with a trend in restoring the heterogeneity of α-diversity and in reducing the percentage of potentially pathogenic microbial species, although this benefit is less evident in patients with cirrhosis. Further studies with larger sample size are necessary to confirm these data.