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Intrahepatic immune changes after hepatitis c virus eradication by direct-acting antiviral therapy

Giuliana Amaddeo1,2,3, Cong Trung Nguyen1,2, Pascale Maillé1,2,4

  • 1INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.

Liver International : Official Journal of the International Association for the Study of the Liver
|August 25, 2019
PubMed
Abstract

Insights

Direct acting anti-virals (DAA) cure hepatitis C virus (HCV) but may alter immune surveillance. This study found minor immune changes in non-tumoral liver tissue after HCV cure, suggesting DAA therapy does not promote liver cancer.

Area of Science:

  • Hepatology
  • Immunology
  • Oncology

Background:

  • Direct acting anti-virals (DAA) have revolutionized hepatitis C virus (HCV) treatment, leading to sustained virological response (SVR).
  • The impact of viral clearance on liver carcinogenesis, particularly concerning intrahepatic immune surveillance, remains debated.
  • This study investigates immune microenvironment alterations post-HCV cure via DAA therapy in patients who developed hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To characterize intrahepatic immune changes following HCV cure induced by DAA therapy.
  • To assess whether viral clearance influences the immune microenvironment in a manner that could promote liver tumor growth.
  • To compare immune profiles in patients with HCC after DAA-induced SVR versus untreated HCV-infected controls.

Main Methods:

  • Included patients with compensated cirrhosis and HCC who achieved SVR after DAA therapy; a control group of untreated HCV patients was selected.
  • Analyzed tumoral and non-tumoral liver tissues using the Nanostring Immuno-Oncology-360 panel for gene expression.
  • Quantified immune cell densities via immunohistochemistry.

Main Results:

  • Non-tumoral tissue analysis revealed a downregulation of interferon-related genes (e.g., MX1, ISG15, IFIT1) after DAA therapy.
  • No significant differences were observed in other immune profiles or immune cell densities between DAA-treated and untreated groups.
  • Intra-tumoral immune profiles of HCCs in patients with DAA-induced SVR were comparable to those in untreated patients.

Conclusions:

  • HCV eradication with DAA therapy primarily results in downregulated interferon-stimulated genes in non-tumoral liver tissues of cirrhotic patients who develop HCC.
  • These observed immune changes are minimal and unlikely to significantly favor HCC occurrence or recurrence post-SVR.
  • The study suggests that DAA therapy-induced viral clearance does not substantially alter the liver immune microenvironment to promote liver carcinogenesis.
Keywords:
direct acting antiviralshepatitis c virushepatocellular carcinomaimmunity

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