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Non-selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels.

Author information

Affiliations

  • 1. Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
      Authors
    • Quinn G 1
    • Ali RO 1
    • Zhang GY 1
    • Hill K 1
    • Townsend E 1
    • Chakraborty M 1
    • Ahmad MF 1
    • Gewirtz M 1
    • Haddad J 1
    • Koh C 1
    • Etzion O 1
    • Heller T 1
    (12 authors)
  • 2. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
      Authors
    • Umarova R 2
    (1 author)
  • 3. Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
      Authors
    • Rosenzweig S 3
    • Rampertaap S 3
    (2 authors)
  • 4. NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
      Authors
    • Schoenfeld M 4
    • Yang S 4
    (2 authors)
  • 5. Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
      Authors
    • Levy E 5
    (1 author)
    • Show all (6)

ORCIDs linked to this article

Show all (7)

Liver International : Official Journal of the International Association for the Study of the Liver, 26 Sep 2023, 43(12):2701-2712
https://doi.org/10.1111/liv.15737 PMID: 37752797 

Abstract 

Background & aims

Direct-acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA therapy is common, little is known about the intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of the gut microbiome and the liver after SVR.

Methods

Twenty-two HCV patients were evaluated before and 9 months after 12 weeks of sofosbuvir/velpatasvir treatment. All achieved SVR. A liver biopsy, portal blood (direct portal vein cannulation), peripheral blood and stool samples were obtained. RNA-seq and immunofluorescent staining were performed on liver biopsies. RNA-seq and 16S rRNA metagenomics were performed on stool.

Results

Differential expression within liver transcription showed 514 downregulated genes (FDR q < .05; foldchange > 2) enriched in inflammatory pathways; of note, GO:0060337, type 1 IFN signalling (p = 8e-23) and GO:0042742, defence response to bacterium (p = 8e-3). Interestingly, microbial products increased in the portal blood and liver after SVR. Due to the increase in microbial products, the gut microbiome was investigated. There was no dysbiosis by Shannon diversity index or Bacteroides/Firmicutes ratio. There was a differential increase in genes responsible for bacterial lipopolysaccharide production after SVR.

Conclusions

The decrease in the antiviral interferon pathway expression was expected after SVR; however, there was an unanticipated decrease in the transcription of genes involved in recognition and response to bacteria, which was associated with increased levels of microbial products. Finally, the alterations in the function of the gut microbiome are a promising avenue for further investigation of the gut-liver axis, especially in the context of the significant immunological changes noted after SVR.

Full text links 

Read article at publisher's site: https://doi.org/10.1111/liv.15737

Read article for free, from open access legal sources, via Unpaywall: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/liv.15737Unpaywall

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Funding 

Funders who supported this work.

NCI NIH HHS

    NIDDK NIH HHS

      NIH Clinical Center

        National Cancer Institute

          National Institute of Diabetes and Digestive and Kidney Diseases