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MYELOID-DERIVED SUPPRESSOR CELLS TWO YEARS AFTER HEPATITIS C VIRUS ERADICATION USING DIRECTLY ACTING ANTIVIRALS
Dania Abunawas1, Amany Abbasy2, Mohamed Afifi3
1Academic fellow, Immunology and Allergy department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Insights
Hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs) does not fully restore immune function, as myeloid-derived suppressor cells (MDSCs) remain elevated two years post-treatment. This indicates a slow immune reconstitution in HCV patients after DAA therapy.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells that significantly contribute to tumor progression and viral escape.
- In chronic Hepatitis C Virus (HCV) infection, elevated MDSCs can suppress T-cell responses, potentially leading to severe infections, tumors, and poor vaccine response.
- The impact of direct-acting antiviral (DAA) therapy on immune function and surveillance capacity in HCV patients remains unclear.
Purpose of the Study:
- To investigate the frequency of M-MDSCs (CD33+, CD11b+, HLA-DR-) in patients with a history of HCV.
- To assess immune recovery 2-3 years after successful virus eradication using DAA therapy.
Main Methods:
- A cohort of 110 subjects was studied, including 55 HCV patients who achieved sustained virologic response (SVR) for 2-3 years post-DAA treatment and 55 age/gender-matched healthy controls.
- Flow cytometry was used to determine the frequencies of MDSCs (CD33+CD11b+HLA-DR-).
Main Results:
- MDSC levels were significantly higher in HCV-treated individuals compared to healthy controls, even over two years after viral eradication (median 5 vs. 3.1, P<0.001).
- These elevated MDSC levels persisted despite normalization of laboratory parameters and absence of liver fibrosis.
Conclusions:
- Successful DAA therapy results in slow and incomplete immunological reconstitution.
- Elevated MDSC levels two years post-HCV eradication suggest persistent immune dysregulation.
- Further research is needed to understand the clinical implications of these findings.
Background:
Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity.
Objective:
The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy.
Methods:
This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed.
Results:
Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001).
Conclusion:
Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.
