Rapid changes in peripheral lymphocyte concentrations during interferon‐free treatment of chronic hepatitis C virus infection

Abstract

Treatment of chronic hepatitis C virus infection with direct acting antivirals results in a rapid decline in viral load and markers of hepatic inflammation, including serum CXCL10 concentration, which is followed in most cases by a sustained virologic response. Whether parallel changes of significance occur in the cellular composition of peripheral blood is relatively unknown. We hypothesized that longitudinal characterization of peripheral blood during treatment would provide insight into cellular migration and immune activation, which would have implications for understanding host immunity both before and after HCV treatment and may relate to HCV clearance. We analyzed longitudinal peripheral innate and adaptive immune cell populations by flow cytometry from 95 subjects enrolled in two direct acting antiviral clinical trials, and examined chemokine receptor expression on T-lymphocytes in 43 patients. Within 1–2 weeks of initiating treatment, significant increases were observed in the concentration of peripheral CD4+ and CD8+ T-lymphocytes, but not monocyte or natural killer cells. In tandem with these changes, the percent of both CD4+ and CD8+ T-lymphocytes with an activated phenotype (HLA-DR+ and CD38+) decreased, and T-lymphocyte surface expression of CXCR3, the chemokine receptor for CXCL10, increased. Conclusion Rapid changes in peripheral cellular populations occur during DAA –treatment of HCV infection, which could potentially relate to hepatic efflux of tissue lymphocytes due to altered inflammation and chemokine receptor signaling, providing critical insight into the relationship between host immunity and viral clearance during hepatitis C virus infection.

Microbial translocation and T cell activation are modified by direct‐acting antiviral therapy in HCV‐infected patients

“…In our study, after direct‐acting antiviral treatment, we found a significant decline in markers of T‐cell activation. A previous study also reported a decline of T‐cells CD38+HLADR+ expression in chronic HCV patients, after interferon‐free treatment …”

“…A previous study also reported a decline of T-cells CD38+HLADR+ expression in chronic HCV patients, after interferon-free treatment. 36 The immunophenotypic analysis was performed only in Group ≥F3, since it is known that the chronic immunosuppressive therapy, as administered in patients in Group LT + ≥F2, could impact on the CD38 expression on T-cells. Indeed, it has been reported that CD38 expression on T-cells is under-expressed after anti-rejection therapy, and its determination has been proposed as assay to be used routinely to quantify the level of immunosuppression in clinical practice.…”

Characterization of changes in intrahepatic immune cell populations during HCV treatment with sofosbuvir and ribavirin

“…In this study, we used a unique collection of paired liver biopsies from patients treated with DAA therapy to ask how a broad array of intrahepatic immune cellular populations change during DAA therapy, and explored whether there were associations with treatment outcome. We consider these findings in the context of prior work showing that multiple peripheral cellular populations change rapidly after DAA therapy, which we hypothesized was due to efflux of intrahepatic lymphocytes as well as reduced de novo migration …”

“…We consider these findings in the context of prior work showing that multiple peripheral cellular populations change rapidly after DAA therapy, which we hypothesized was due to efflux of intrahepatic lymphocytes as well as reduced de novo migration. 16…”

Direct‐acting antiviral drugs are triggers for psoriasis: report of three cases

“…The reactions can be explained by direct immunological drug effects or by immuno‐infectious changes (“reconstitution” syndrome with DAAs). 7,10 The latter is a hypothesis, which could be supported based on some studies that highlighted the relation between HCV viremia in T‐cell activation and the roles of interferon‐gamma (IFN‐γ), interleukin (IL)‐17, and IL‐22 producing T helper (Th1, Th17, and Th22) cells in HCV infection . These cytokines can have a significant decrease after DAA therapy, and some are also a target for psoriasis treatment.…”