Adenugba, Akinbami and Hornung, Matthias and Weigand, Kilian and Peschel, Georg and Junger, Henrik and Kupke, Paul and Lang, Hauke and Marquardt, Jens U. and Zimmermann, Tim and Geissler, Edward K. and Schlitt, Hans J. and Werner, Jens M. (2021) Ribavirin Improves NK Cell IFN gamma Response During Sofosbuvir-based DAA Therapy in HCV-infected Liver Transplant Recipients. TRANSPLANTATION, 105 (10). pp. 2226-2238. ISSN 0041-1337, 1534-6080
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Background. Chronic hepatitis C virus (HCV) infection is characterized by activation of natural killer (NK) cells. Here, we asked whether HCV elimination by sofosbuvir-based direct-acting antivirals (DAAs) and the addition of ribavirin (RBV) improve NK cell function in liver transplant (LTx) recipients. Methods. We analyzed NK cell degranulation and interferon (IFN)gamma-response along with STAT1 and STAT4 phosphorylation in 29 HCV-infected LTx recipients and 17 HCV-infected patients during DAA treatment. Results. Compared with uninfected LTx recipients, NK cells from HCV-infected LTx recipients were polarized toward cytotoxicity with increased CD107a-degranulation (10.1% versus 14.6%; P = 0.0263) and reduced capacity to produce IFN gamma (43.0% versus 26.7%; P = 0.0002). The altered phenotype of NK cells in HCV-infected LTx recipients was accompanied by increased STAT1 (44.6% versus 87.4%; P < 0.0001) and STAT1 phosphorylation (0.7% versus 8.9%; P = 0.0005) compared with pSTAT4 IFN alpha-induction (29.9% versus 17.6%; P = 0.0014). Successful DAA therapy did not affect CD107a-degranulation but decreased STAT1. RBV cotreatment with DAA therapy for HCV increased CD56(Bright) NK cell IFN gamma-responses in LTx recipients (70.9% versus 89.2%; P = 0.002), and this correlated to an increase in the inducibility of pSTAT4 (MFI 157 versus 173; P = 0.0002). Conclusions. RBV cotreatment of HCV infection improved pSTAT4-dependent IFN gamma-production in NK cells. This is relevant especially for immunocompromised patients such as LTx recipients or patients with end-stage liver disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; ACTING ANTIVIRAL THERAPY; INNATE; IMPACT; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Sep 2022 05:32 |
| Last Modified: | 05 Sep 2022 05:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46500 |
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