Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma...

Area of Science:

• Hepatology
• Virology
• Oncology

Background:

• Hepatitis C virus (HCV) infection is a primary cause of hepatocellular carcinoma (HCC), accounting for about 30% globally.
• Antiviral treatment leading to sustained virological response (SVR) significantly reduces HCC risk, yet HCC can still develop in treated chronic hepatitis C (CHC) patients.
• The incidence of HCC post-SVR is rising in the direct-acting antiviral (DAA) era, suggesting persistent risk factors.

Purpose of the Study:

• To review the molecular mechanisms underlying HCC development after HCV eradication.
• To identify key risk factors contributing to post-SVR HCC.
• To discuss optimal HCC surveillance strategies for CHC patients achieving SVR.

Main Methods:

• Literature review focusing on molecular mechanisms, risk factors, and surveillance strategies for HCC in CHC patients post-SVR.
• Analysis of factors including liver background, immune dysregulation, epigenetic changes, and genetic predispositions.
• Discussion of risk stratification and surrogate markers for HCC surveillance.

Main Results:

• Persistent liver inflammation, fibrosis, immune dysregulation, epigenetic alterations, and genetic factors contribute to HCC development post-SVR.
• The increasing proportion of HCC post-SVR highlights the need for continued vigilance.
• Risk stratification and surrogate markers are essential for targeted HCC surveillance.

Conclusions:

• HCV eradication is effective but does not fully negate HCC risk in CHC patients.
• Ongoing monitoring and risk assessment are necessary for early detection of HCC in high-risk individuals post-SVR.
• Further research into molecular pathways and improved surveillance tools is warranted.