Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103. CD69 + CD8+ T cells expressed low levels of S1PR1 and KLF2 and a large proportion (>90%) was CXCR6+, resembling liver TRM in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69 + CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69 + CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69 + CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69 + CD8+ T cells likely TRM which have a reduced cytolytic potential. In patients with chronic viral hepatitis TRM have a distinct phenotype.

CD69

Granzyme A

10.1038/s41598-017-06352-3

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Citations (93)

MR Elastography of the Liver: Defining Thresholds for Detecting Viscoelastic Changes

Radiology (2013)

Anneloes E. Bohte Philippe Garteiser A. de Niet P.F.C. Groot Ralph Sinkus

Purpose To define thresholds for detecting significant change in liver viscoelasticity with magnetic resonance (MR) elastography, both for whole-liver measurements and for voxel-wise measurements in relation to spatial resolution. Materials and Methods This prospective study was approved by the institutional review board, and all participants provided written informed consent. Thirty participants (16 volunteers and 14 patients with hepatitis B or C; 18 men; median age, 30.4 years; age range, 18.9–58.6 years) underwent imaging twice while in the same position (intraimage reproducibility), after repositioning (within-day reproducibility), and 1–4 weeks later (between-weeks reproducibility). MR elastography parameters comprised elasticity, viscosity, attenuation parameter α, and propagation parameter β. Bland-Altman analysis was used to calculate repeatability indexes for each parameter. Analyses were performed in a region-of-interest and a voxel-by-voxel level. Voxel-wise results were calculated in relation to spatial resolution by applying Gaussian filtering to establish the optimal trade-off point between resolution and reproducibility. Results For elasticity, α, and β, within-day and between-weeks results were significantly lower than intraimage results (P ≤ .018 for all). Within-day and between-weeks results did not differ significantly. Over-time changes of more than 22.2% for elasticity, 26.3% for viscosity, 26.8% for α, and 10.1% for β represented thresholds for significant change. The optimal trade-off between spatial resolution and reproducibility was found at a filter size of 8-mm full width at half maximum (FWHM) for elasticity and propagation parameter β and at 16-mm FWHM for viscosity and attenuation parameter α. Conclusion Repositioning causes a significant decrease in the reproducibility of MR elastography. The propagation parameter β is the most reliable parameter, with an over-time threshold for significant change of 10.1% and the ability to reproduce viscoelasticity up to a resolution of 8-mm FWHM. ©RSNA, 2013 Online supplemental material is available for this article.

Repeatability

Elasticity

Magnetic Resonance Elastography

10.1148/radiology.13122669

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Citations (3)

Genetic variation in IL28B and treatment outcome in HBeAg-positive and -negative chronic hepatitis B patients treated with Peg interferon alfa-2a and adefovir

Scandinavian Journal of Gastroenterology (2012)

A. de Niet R. Bart Takkenberg Ryma Benayed Bridget Riley‐Gillis Christine J. Weegink

In a cohort of 95 chronic hepatitis B patients, who were treated with peg-interferon and adefovir for 1 year, and who had 15% HBsAg loss (overall), no association was found between IL28B polymorphisms and HBeAg seroconversion or HBsAg clearance. These findings suggest that any association with outcome, if present, is less than that seen in chronic hepatitis C. Additional studies are needed to enlarge sample size and to refine our understanding of IL28B biology in the context of chronic hepatitis B response to immunomodulatory and direct antiviral therapy.

Adefovir

Seroconversion

Pegylated interferon

HBeAg

10.3109/00365521.2011.648952

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Citations (31)

MR Elastography of the Liver: Defining Thresholds for Detecting Viscoelastic Changes

Radiology (2013)

Anneloes E. Bohte Philippe Garteiser A. de Niet P.F.C. Groot Ralph Sinkus

To define thresholds for detecting significant change in liver viscoelasticity with magnetic resonance (MR) elastography, both for whole-liver measurements and for voxel-wise measurements in relation to spatial resolution.This prospective study was approved by the institutional review board, and all participants provided written informed consent. Thirty participants (16 volunteers and 14 patients with hepatitis B or C; 18 men; median age, 30.4 years; age range, 18.9-58.6 years) underwent imaging twice while in the same position (intraimage reproducibility), after repositioning (within-day reproducibility), and 1-4 weeks later (between-weeks reproducibility). MR elastography parameters comprised elasticity, viscosity, attenuation parameter α, and propagation parameter β. Bland-Altman analysis was used to calculate repeatability indexes for each parameter. Analyses were performed in a region-of-interest and a voxel-by-voxel level. Voxel-wise results were calculated in relation to spatial resolution by applying Gaussian filtering to establish the optimal trade-off point between resolution and reproducibility.For elasticity, α, and β, within-day and between-weeks results were significantly lower than intraimage results (P ≤ .018 for all). Within-day and between-weeks results did not differ significantly. Over-time changes of more than 22.2% for elasticity, 26.3% for viscosity, 26.8% for α, and 10.1% for β represented thresholds for significant change. The optimal trade-off between spatial resolution and reproducibility was found at a filter size of 8-mm full width at half maximum (FWHM) for elasticity and propagation parameter β and at 16-mm FWHM for viscosity and attenuation parameter α.Repositioning causes a significant decrease in the reproducibility of MR elastography. The propagation parameter β is the most reliable parameter, with an over-time threshold for significant change of 10.1% and the ability to reproduce viscoelasticity up to a resolution of 8-mm FWHM. Online supplemental material is available for this article.

Repeatability

Elasticity

Magnetic Resonance Elastography

10.1148/radiol.13122669

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Citations (35)

The role of children in the transmission of mild SARS‐CoV‐2 infection

Acta Paediatrica (2020)

A. de Niet Bart L. Waanders Iris Walraven

No potential conflicts of interest relevant to this article are reported.

2019-20 coronavirus outbreak

Sars virus

Betacoronavirus

10.1111/apa.15310

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Citations (8)