After the Storm: Persistent Molecular Alterations Following HCV Cure

Coline Seurre1,2, Armando Andres Roca Suarez1,2, Barbara Testoni1,2

  • 1INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France.

Insights

Direct-acting antivirals (DAAs) can eliminate hepatitis C virus (HCV), but challenges remain. HCV cure does not fully resolve liver cell alterations, increasing cancer risk, necessitating further research.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Hepatitis C virus (HCV) infection poses significant global health challenges despite advances in treatment.
  • Direct-acting antivirals (DAAs) achieve high viral clearance rates but do not fully reverse disease-associated cellular changes.
  • HCV-cured individuals remain at elevated risk for liver complications, including hepatocellular carcinoma.

Purpose of the Study:

  • To review the impact of HCV infection on peripheral and intrahepatic cells.
  • To summarize persistent cellular alterations after DAA treatment.
  • To explore molecular mechanisms behind long-term cell changes and potential chemo-preventive strategies.

Main Methods:

  • Literature review focusing on cellular and molecular changes in HCV infection and treatment.
  • Analysis of existing data on cell population dynamics and alterations post-DAA therapy.
  • Discussion of emerging single-cell multiomics technologies for disease understanding.

Main Results:

  • HCV infection profoundly affects diverse cell populations, both in the liver and periphery.
  • DAA treatment, while clearing the virus, leaves residual cellular and molecular abnormalities.
  • Persistent alterations in intrahepatic cells may underlie the continued risk of liver disease progression.

Conclusions:

  • HCV eradication via DAAs is a major therapeutic advance but does not eliminate all disease risks.
  • Understanding persistent cellular alterations is crucial for managing long-term complications.
  • Single-cell multiomics offers promising avenues for developing novel chemo-preventive strategies against HCV-related liver cancer.