Effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells in patients with chronic hepatitis C / 中华传染病杂志

ABSTRACT

Objective To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients.Methods A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017.The peripheral blood mononuclear cells ( PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy , at four weeks after DAA therapy , at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy.The frequencies of MDSC and M-MDSC were detected by the flow cytometer.The t test, U test and chi-square test was employed to analyze the data.Results All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed . Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z＝-4.593, P＜0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r＝0.688, P＜0.01) and aspartate aminotransferase (r＝0.735, P＜0.01).After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls ( Z＝-1.221, P＞0.05).However, at 12 weeks after DAA therapy , the MDSC frequency increased , with statically significance compared to the controls (1.64%vs 0.60%, Z＝-3.117, P＝0.002).At 12 weeks after the end of DAA therapy , the MDSC frequency had decreased to 1.29%again, with no statistical significance compared to the controls ( Z ＝-1.387, P ＝0.664).The changes of M-MDSC frequency were slightly different.Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66%vs 0.81%, Z＝-2.745, P＜0.01).The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy , respectively.The differences were not statistically significant compared to the controls (Z＝-0.589,-1.028 and -0.486, respectively, all P＞0.05).Conclusion Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.