Restoration of the gut-microbiota-liver axis after hepatitis C virus eradication.

Abstract

Background & aims: We previously reported altered intestinal environmental features during HCV infection. Here, we aimed to characterize the gut-microbiota-liver axis in patients with chronic hepatitis C after a sustained virological response (SVR).

Methods: A total of 174 patients with HCV infection were enrolled in a cross-sectional study: 95 with chronic hepatitis (CH-HCV group) and 79 with cirrhosis or hepatocellular carcinoma (LC/HCC-HCV group). In addition, 75 post-SVR patients were included (CH-SVR group, n = 29; LC/HCC-SVR group, n = 46), along with 23 healthy individuals. A longitudinal study was subsequently conducted on 49 patients (CH, n = 29; LC/HCC, n = 20) with SVR at 24 and 48 weeks after the end of treatment. RNA sequencing was performed on 65 patients with HCV infection, 28 post-SVR patients, and 12 healthy controls.

Results: In the cross-sectional analysis, HCV eradication was associated with partial restoration of the dysbiotic gut microbiota, including reduced streptococcal overgrowth and an increase in the potentially beneficial genus Blautia, approaching levels seen in healthy individuals. Additionally, the aberrant fecal bile acid profile showed rebalancing, accompanied by restored expression of genes involved in the classical pathway of cholic and chenodeoxycholic acid biosynthesis. In the longitudinal study, improvements in liver fibrosis and function - evidenced by decreased Fibrosis-4 index and alanine aminotransferase levels - were significantly correlated with increased abundance of Blautia (p <0.0001 and p = 0.0344, respectively), suggesting a beneficial role in liver recovery.

Conclusion: The gut-microbiota-liver axis is partially restored following HCV eradication, with recovery from liver damage associated with the resurgence of commensal Lachnospiraceae species.

Impact and implications: This study offers significant insights into the gut-microbiota-liver axis in patients with chronic hepatitis C following a sustained virological response. The findings demonstrate that HCV eradication promotes partial restoration of the dysbiotic gut microbiota, particularly an increase in the beneficial genus Blautia, as well as a rebalancing of the fecal bile acid profile. These changes are closely associated with significant improvements in liver fibrosis and function, highlighting a potential role of the gut microbiota in liver recovery and regeneration.