The Institute for Basic Science (IBS) Korea Virus Research Institute’s (KVRI) Center for Viral Immunology, led by Director SHIN Eui-Cheol, has made a groundbreaking discovery regarding the lasting effects of chronic Hepatitis C virus (HCV) infection on the immune system. Even after successful treatment, traces of “epigenetic scars” in regulatory T cells continue to exhibit sustained inflammatory properties in the body. This research sheds light on the importance of understanding and addressing these long-term effects for the overall health and well-being of patients.
Chronic hepatitis C, caused by the hepatitis C virus, is a serious condition that can lead to severe complications such as liver cirrhosis and liver cancer. While the development of highly effective direct-acting antivirals (DAAs) has significantly increased cure rates for this chronic viral infection, it has been observed that the immune system does not fully recover even after the virus is eliminated.
The study conducted by the research team focused on patients with chronic HCV infection who achieved sustained virologic response (SVR) after DAA treatment. SVR indicates that the virus is no longer detectable in the blood for 12 weeks post-treatment, confirming successful eradication of the virus. However, the researchers found that the frequency of activated TREG cells remained elevated during treatment and persisted even after viral clearance.
Using advanced techniques such as RNA sequencing and ATAC-seq, the team analyzed the transcriptomic and epigenetic profiles of TREG cells from HCV patients post-treatment. They discovered that inflammatory features, including increased TNF signaling, were still present in these cells, indicating long-lasting immune system alterations caused by the chronic infection. Even after the virus was no longer detectable, the activated TREG cells continued to produce inflammatory cytokines, suggesting ongoing immune dysregulation.
Monitoring the patients for up to six years after achieving SVR revealed that the inflammatory features in TREG cells persisted over time. This finding has significant implications for the long-term management of patients treated for chronic HCV infection, as the potential for chronic inflammation and related health issues remains a concern.
Director SHIN Eui Cheol emphasized the importance of ongoing monitoring post-treatment, stating, “Our research highlights the need for continued vigilance even after successful clearance of HCV. By understanding the underlying mechanisms of these persistent immune changes, we can develop more effective strategies to support complete recovery and enhance the quality of life for patients.”
The research team is now focused on unraveling the mechanisms behind the sustained inflammatory state of TREG cells and exploring potential therapeutic interventions to reverse these epigenetic and transcriptomic changes. Director Shin expressed interest in investigating whether other chronic viral infections also induce long-lasting immune alterations and their clinical implications.
This groundbreaking research was recently published in the Journal of Hepatology, showcasing the team’s innovative contributions to advancing our understanding of chronic viral infections and their impact on the immune system. The insights gained from this study have the potential to revolutionize the way we approach the long-term care of patients with chronic HCV infection, paving the way for improved health outcomes and a better quality of life.
