After the Storm: Persistent Molecular Alterations Following HCV Cure

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.