Influence of Hepatitis C Virus Eradication With Direct-acting Antivirals on the Gut Microbiota in Patients With Cirrhosis

Francesca Romana Ponziani; Lorenza Putignani; Francesco Paroni Sterbini; Valentina Petito; Anna Picca; Federica Del Chierico; Sofia Reddel; Riccardo Calvani; Emanuele Marzetti; Maurizio Sanguinetti; Antonio Gasbarrini; Maurizio Pompili

Disclosures

Aliment Pharmacol Ther. 2018;48(11-12):1301-1311. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

The modifications of the gut-liver axis are the mainstay of liver cirrhosis and are involved in the liver injury independently from the aetiology of the disease.[1–3] Increased intestinal permeability, an overgrowth of potentially pathogenic bacteria (eg, Staphylococcaeae, Enterobacteriaeceae, and Enterococcaceae) and a reduction of those beneficial for the organism (eg, Lachnospiraceae, Ruminococcaceae, and Clostridia cluster XIV) are typically reported in cirrhotic patients. These changes are closely correlated with the stage of the disease and some outcomes such as the occurrence of clinically significant liver-related events and the number of hospital admissions.[1–3]

In patients with chronic hepatitis C virus (HCV) infection the circulating level of lipopolysaccharides (LPS) is increased, suggesting that microbial translocation is involved in liver inflammation and injury thus contributing to disease progression.[4,5] Moreover, HCV infection is associated with an altered gut microbiota profile,[6,7] though a recent cross-sectional study failed to demonstrate any significant improvement in systemic inflammation, endotoxemia, and gut microbiota composition in patients who achieved a sustained virological response (SVR) after treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV).[8]

The recent introduction of direct-acting antiviral (DAA) therapy has dramatically changed the rates of cure of HCV infection even in difficult to treat subjects and in those with severe comorbidities.[9] A growing number of studies[10–14] have also demonstrated an improvement in liver stiffness, which is a surrogate marker of liver fibrosis, after HCV eradication. This may have a beneficial impact on the gut-liver axis in these patients and may further contribute to slowing down the progression of the disease, potentially influencing the future occurrence of complications. However, so far, there is no longitudinal investigation on the effects of the cure of HCV infection on the gut-liver axis, and whether these possible changes are associated with clinical outcomes remains to be demonstrated.

This study investigated the modifications in the gut microbiota composition occurring after HCV infection eradication with DAA therapy, the possible change in the inflammatory state and intestinal permeability, and delineated its correlation with liver disease-associated outcomes.

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