Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR−/low cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = −2.438, P = 0.015), while there was no statistical difference between the frequency of HLA-DR−/lowCD33+CD11b+CD15+ (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = −2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree.

Dysregulation of the host immune responses induced by host hepatitis B virus (HBV)interactions has been observed in acute-on-chronic liver failure (ACLF). Myeloid-derived suppressor cells (MDSCs), well known for their immunomodulatory properties, can suppress T-cell function by regulating the expression of CD3 ζ chain in cancer and autoimmune/infectious diseases while rarely have been studied in ACLF. In this study, MDSCs, CD4 + /CD8 + T cells, and CD3 ζ chain were analyzed by flow cytometry in peripheral blood mononuclear cells obtained from HBV-related ACLF patients, chronic hepatitis B (CHB) patients and healthy controls. ACLF patients were followed up for dynamic detection of MDSCs and observation of outcomes after treatment. Interestingly, peripheral CD14 + CD33 + CD11b + HLA-DR −/low MDSCs from ACLF patients were significantly increased compared to those from CHB patients and healthy controls.CD4 + /CD8 + T cell frequency and CD3 ζ chain expression in T cells were decreased in ACLF patients compared to those of healthy controls and were negatively correlated with matched MDSC frequency. Meanwhile, the frequency of MDSCs was closely correlated with biochemical parameters that are relevant for liver injury rather than virological parameters. Moreover, a lower level of MDSCs was correlated with a better short-term prognosis (within 4 weeks but not at 8 weeks), and MDSCs remained high in ACLF patients whose conditions worsened within a 4-week follow-up period after treatment. These results suggest that MDSCs are closely involved in cell-mediated immunity in HBV-related ACLF and that peripheral MDSC expansion is closely associated with disease severity and progression in HBV-related ACLF, which may serve as a predictor of short-term prognosis. K E Y W O R D S cell-mediated immunity, hepatitis B virus, immunomodulation 1 | INTRODUCTION As a global health problem, especially in Asia, there are over 350 million people chronically infected with hepatitis B virus (HBV) worldwide, and approximately 22 million people suffer from chronic hepatitis B (CHB) virus in China. 1 HBV infection can lead to a spectrum of liver diseases, including being a chronic asymptomatic HBV carrier (AsC) or developing CHB, liver cirrhosis, hepatocellular carcinoma, and acute-on-chronic liver failure (ACLF). 2,3 The occurrence of ACLF often represents a complicated state of host immune J Med Virol. 2019;91:1510-1518. wileyonlinelibrary.com/journal/jmv

Objective Up to now, little was known about the immunological changes of chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAAs); we try to explore the effect of DAAs on the frequency of monocytes, NK cells, and cytokines that promote their activation. Methods 15 treatment-naive CHC patients and 10 healthy controls were recruited. Patients were examined before DAAs therapy (0 w) and at week 4 (4 w) and week 12 (12 w) of therapy. Percentage of monocytes and NK cells of the peripheral blood was analyzed by flow cytometry. Serum cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 were measured by enzyme linked immunosorbent assay. Results The frequency of CD3–CD16+CD56+ NK cells and classic CD14++CD16− monocytes decreased, while CD14+CD16+ monocytes and cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 increased at 0 w compared to healthy controls. During DAAs treatment, the decreased NK cells and classic monocytes gradually increased to normal levels; the increased inflammatory monocytes and cytokines IL-12 and CXCL11 decreased to normal levels, but the increased cytokines IL-18, CXCL10, sCD14, and sCD163 still remained at high levels at 12 w though they decreased rapidly from 0 w. Conclusion Our results showed that DAAs treatment attenuated the activation of monocytes and NK cells in CHC patients. Trial registration number is NCT03063723.

Currently, hepatitis C antiviral therapy is entering a new era with the use of direct-acting antiviral (DAA) agents. However, the precise immunological influences of DAA therapy in patients with chronic hepatitis C (CHC) are insufficiently understood. This study aimed to investigate the effects of DAA therapy on the frequency of myeloid-derived suppressor cells (MDSCs), T lymphocytes, and natural killer (NK) cells in patients with CHC. Thirty-two treatment-naive CHC patients were treated with DAA therapy, and the frequency of immune cells was analyzed by flow cytometry at various time points during and after therapy. Sixteen healthy donors were recruited for comparison. DAA therapy decreased the frequency of MDSCs and monocytic MDSCs in patients with CHC to a normal level. DAA therapy also increased the CD8 T and NK cell levels in patients with CHC. In addition, activation (NKp30 and NKp46) and inhibitory (NKG2A) receptors on NK cells were downregulated to yield an NK cell phenotype resembling that observed in the healthy controls. This study provides insight into the normalization of immune cell levels under DAA therapy and indicates that restoration of the immune system in patients with CHC strongly supports long-term curative hepatitis C virus eradication.

This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1‐year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono‐therapy. An HBsAg titer of <0.05 IU/ml was defined as a “functional cure.” In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN‐γ (after Week 0), and IL‐22 and IP‐10 (after Week 12). In the non‐cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN‐γ (after Week 12), and a probability of increasing IP‐10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL‐10, IL‐23, CCL‐3, IL‐1β, IL‐2, and IL‐12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non‐cured group. The frequencies of T cells expressing Tim‐3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono‐therapy group. Changes in cytokine levels (IFN‐γ, IP‐10, IL‐10, IL‐23, CCL‐3, IL‐1β, IL‐2, and IL‐12P70) and T cell surface molecules (CD45RO+) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from Weeks 12 to 24 during sequential interferon therapy may be a critical time of immune status change.