Restoration of natural killer cell activity by pegylated interferon‐alpha/ribavirin therapy in chronic hepatitis <scp>C</scp> patient

Nakamura, Ikuo; Asano, Takeharu; Asabe, Shinichi; Ando, Mayumi; Sano, Tsuyoshi; Miyata, Yuki; Taira, Junichi; Sugimoto, Katsutoshi; Imai, Yumiko; Imawari, Michio

doi:10.1111/hepr.12322

Cited by 6 publications

(11 citation statements)

References 23 publications

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“…In this study, the frequency of CD56 dim NK cells was revealed to be increased by DAA therapy. However, PEG/RBV therapy induced an increase in the frequency of CD56 bright NK cells . Therefore, PEG/RBV therapy might affect the increase in the frequency of CD56 bright NK cells.…”

Section: Discussionmentioning

confidence: 98%

“…Hepatitis C virus infection is reported to reduce NK cell activity . We have already reported that PEG/RBV therapy could restore NK cell activity in CH(C) patients with SVR . The restoration of NK cell activity was speculated to be due to a decline of HCV load by the therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Just before the initiation of the DAA therapy (0M), at the completion of the therapy (EOT), and at 24 weeks after completion of the therapy (AFTER), NK cell activity was estimated by Cr release assay as previously reported …”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the frequency of NK (CD3 − /CD56 + ), CD56 dim NK, and CD56 bright NK cells in peripheral blood were estimated by flow cytometry at 0M, EOT, and AFTER, as previously reported . The patients were divided in two groups according to the value of their Fib‐4 index, and the NK cell activity ratio (AFTER/0M) were statistically analyzed using the Mann–Whitney U ‐test between the two groups.…”

Section: Methodsmentioning

confidence: 99%

“…We have already reported that PEG/RBV therapy could restore NK cell activity in CH(C) patients with SVR . So far, only a few studies on the change in innate immune responses by IFN‐free DAA therapy in CH(C) patients have been carried out.…”

Section: Introductionmentioning

confidence: 99%

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Restoration of natural killer cell activity by interferon‐free direct‐acting antiviral combination therapy in chronic hepatitis C patients

Nakamura

Furuichi

Sugimoto

2018

Hepatology Research

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Restoration of natural killer cell activity by interferon‐free direct‐acting antiviral combination therapy in chronic hepatitis C patients

Nakamura

Furuichi

Sugimoto

2018

Hepatology Research

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Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C

Mania

Kaczmarek

Kemnitz

et al. 2017

Med Microbiol Immunol

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Treatment with pegylated interferon-α and ribavirin (PEG–IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG–IFN/RBV treatment response. Study included 26 children with CHC—13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG–IFNα-2b (60 μg/m2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.

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Model of the adaptive immune response system against HCV infection reveals potential immunomodulatory agents for combination therapy

Obaid

Naz

Ikram

et al. 2018

Sci Rep

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A regulated immune system employs multiple cell types, diverse variety of cytokines and interacting signalling networks against infections. Systems biology offers a promising solution to model and simulate such large populations of interacting components of immune systems holistically. This study focuses on the distinct components of the adaptive immune system and analysis, both individually and in association with HCV infection. The effective and failed adaptive immune response models have been developed followed by interventions/perturbations of various treatment strategies to get better assessment of the treatment responses under varying stimuli. Based on the model predictions, the NK cells, T regulatory cells, IL-10, IL-21, IL-12, IL-2 entities are found to be the most critical determinants of treatment response. The proposed potential immunomodulatory therapeutic interventions include IL-21 treatment, blocking of inhibitory receptors on T-cells and exogenous anti-IL-10 antibody treatment. The relative results showed that these interventions have differential effect on the expression levels of cellular and cytokines entities of the immune response. Notably, IL-21 enhances the expression of NK cells, Cytotoxic T lymphocytes and CD4+ T cells and hence restore the host immune potential. The models presented here provide a starting point for cost-effective analysis and more comprehensive modeling of biological phenomenon.

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Restoration of natural killer cell activity by pegylated interferon‐alpha/ribavirin therapy in chronic hepatitis C patient

Abstract: PEG IFN/RBV therapy in CHC patients could improve NK activity by increasing the frequency of CD56(bright) NK cells in SVR patients. Our study also revealed that eradication of HCV could restore NK-cell activity.

Cited by 6 publications

References 23 publications

Restoration of natural killer cell activity by interferon‐free direct‐acting antiviral combination therapy in chronic hepatitis C patients

Restoration of natural killer cell activity by interferon‐free direct‐acting antiviral combination therapy in chronic hepatitis C patients

Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C

Model of the adaptive immune response system against HCV infection reveals potential immunomodulatory agents for combination therapy

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