[Hepatitis C virus infection and hepatocarcinogenesis]

Area of Science:

• Hepatology
• Virology
• Oncology

Background:

• Hepatitis C virus (HCV) infection is a major global health concern, causing millions of new infections and hundreds of thousands of deaths annually due to complications like cirrhosis and hepatocellular carcinoma (HCC).
• HCV infection contributes to liver cancer through microenvironmental changes, chronic inflammation, oxidative stress, and endoplasmic reticulum stress, potentially involving genetic and epigenetic alterations.
• The direct oncogenic properties of four HCV proteins (core, NS3, NS4B, NS5A) are well-established, highlighting the virus's role in cancer development.

Purpose of the Study:

• To review existing literature on the occurrence of HCC in patients treated with direct-acting antiviral (DAA) therapies.
• To highlight the need for further research into the potential association between DAA therapy and HCC development.
• To emphasize the importance of ongoing HCC surveillance in patients who have achieved a sustained viral response (SVR) after antiviral treatment.

Main Methods:

• A review of publications focusing on HCC occurrence in patients undergoing DAA therapies.
• Analysis of the impact of effective antiviral therapies, including interferon-based treatments and DAAs, on HCV-related mortality and HCC risk.
• Discussion of the necessity for prospective, multicentric studies with extended follow-up periods.

Main Results:

• Effective antiviral therapy, leading to sustained viral response (SVR), significantly decreases HCV-related mortality.
• Interferon-based therapy has been shown to reduce the risk of HCC development.
• While DAAs offer high efficacy and fewer side effects, some publications report unexpected effects, including potential associations with HCC, necessitating further investigation.

Conclusions:

• Antiviral therapy, particularly DAAs, is crucial for reducing HCV-related morbidity and mortality.
• Despite the efficacy of DAAs, there is a need for prospective, multicentric studies to thoroughly examine the risk of HCC formation.
• Post-antiviral therapy HCC surveillance, including regular abdominal ultrasound, remains critical for patients in SVR to detect early signs of liver cancer.