Persistent Epigenetic Changes in Immune Cells Following Hepatitis C Recovery

Hepatitis C virus (HCV) infection may have a long-lasting inflammatory impact at the phenotypic, transcriptomic, and epigenetic level even after treatment success. Researchers from the Institute of Basic Science at the Korea Virus Research Institute’s Center for Viral Immunology observed traces of “epigenetic scars” on peripheral blood regulatory T (TREG) cells, indicating the potential for HCV to alter gene expression and cellular function. The findings emphasize the need for further investigations to determine the long-term clinical outcomes for patients recovered from chronic HCV infection.

The persistent inflammatory features left over from HCV suggest that patients may be at risk for ongoing immune system dysregulation leading to other health concerns. Image Credit: © eddows - stock.adobe.com

HCV is a viral infection contracted through contact with blood from an individual with the virus, resulting in severe inflammation of the liver leading to cirrhosis, liver cancer, and liver failure. The infection starts with an acute phase, which often goes undiagnosed because symptoms of HCV can take years to manifest, and a chronic phase characterized by long-term infection, called chronic HCV. Symptoms of HCV, including muscle aches, fatigue, jaundice, dark-colored urine, and swelling of the legs, typically appear only after the virus has damaged the liver enough to cause them. There are 7 genotypes and 67 subtypes of the infection, of which type 1 is the most common in the US.¹

Despite the severity and difficult diagnosis of HCV, it is a curable condition that patients can recover from. Standard-of-care treatments for HCV are direct-acting antiviral (DAA) tablets, which have proven to be the safest and most efficacious medications for curing this infection. The tablets are typically taken for 8 to 12 weeks, depending on the type of HCV, and patients are advised to receive regular blood tests to ensure the treatment is working. If the test shows no sign of the virus 12 to 24 weeks after completing treatment, this indicates the treatment was successful, referred to as sustained virologic response (SVR).¹

However, the findings from researchers in Korea found that the immune system does not fully recover from HCV and they observed elevated levels of activated TREG cells even after SVR. They performed a comprehensive analysis of patients with chronic genotype 1b HCV who had received SVR by DAA treatment. Using cytometry analysis, RNA sequencing, and ATAC-seq, they investigated the phenotypic, transcriptomic, and epigenetic characteristics, respectively, of TREG cells.^2,3

According to the data, RNA sequencing revealed that activated TREG cells were expanded in peripheral blood during HCV infection and sustained even after viral clearance. This was evident through the presence of signals associated with tumor necrosis factor (TNF) and release of inflammatory cytokines such as IFN-y and IL-17A. Additionally, through ATAC-seq, the researchers noticed that TREG cells underwent epigenetic changes associated with inflammation, indicating a lasting impact on cell regulation and function. The persistent inflammatory features left over from HCV suggest that patients may be at risk for ongoing immune system dysregulation leading to chronic inflammation and other health concerns.^2,3

“Our findings highlight the need for ongoing monitoring even after HCV has been cleared,” said Shin Eui Cheol, MD, PhD, professor at the graduate school of medical science and engineering at Korea Advanced Institute of Science and Technology, and director of the study, said in a press release. “By understanding the underlying mechanisms of these persistent immune changes, we can develop more effective strategies to ensure complete recovery and improve the quality of life for HCV patients.”³

References

1. Hepatitis C. Mayo Clinic. August 23, 2023. Accessed July 25, 2024. https://www.mayoclinic.org/diseases-conditions/hepatitis-c/symptoms-causes/syc-20354278

2, Kim S, Koh J, Lee D, et al. Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals. J Hepatol. June 13, 2024. doi:10.1016/j.jhep.2024.06.011

3. Hepatitis C leaves “scars” in immune cells even after successful treatment. News Release. July 9, 2024. Accessed July 25, 2024. https://www.eurekalert.org/news-releases/1050713