Similar frequencies, phenotype and activation status of intrahepatic NK cells in chronic HBV patients after long-term treatment with tenofovir disoproxil fumarate (TDF)

Tjwa, Eric T.; Zoutendijk, Roeland; Oord, Gertine W. van; Boeijen, Lauke L.; Reijnders, Jurriën G.P.; Campenhout, Margo J.H. van; Knegt, Robert J. de; Janssen, Harry L.A.; Woltman, Andrea M.; Boonstra, André

doi:10.1016/j.antiviral.2016.05.016

Cited by 17 publications

(13 citation statements)

References 17 publications

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“…It should be noted here that for a relevant assessment of clinical parameters of the patients included, a larger cohort of patients would be necessary. As previously described at the protein level in both cellular compartments, the immune profiles in blood and liver of chronic hepatitis B patients exhibit considerable variation: only small gene clusters (<20 genes) were modulated in the same direction in 2 individual patients (Fig. ).…”

Section: Resultssupporting

confidence: 61%

“…This is very clear in case of infections of the liver with hepatitis B virus (HBV) or hepatitis C virus: most studies have examined peripheral blood. Importantly, the few studies that examined the liver demonstrated that the phenotype and function of intrahepatic immune cells differ considerably to that of their peripheral counterparts . In recent years, an increasing number of viral hepatitis researchers are describing efforts to fill this gap of knowledge, and are in agreement that a better understanding of liver immunology is crucial for the development of new curative antiviral treatment strategies for chronic hepatitis B .…”

Section: Introductionmentioning

confidence: 99%

“…c 2018 The Authors Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology and function of intrahepatic immune cells differ considerably to that of their peripheral counterparts. [1][2][3][4][5] In recent years, an increasing number of viral hepatitis researchers are describing efforts to fill this gap of knowledge, and are in agreement that a better understanding of liver immunology is crucial for the development of new curative antiviral treatment strategies for chronic hepatitis B. 1,[5][6][7] Unfortunately, progress in the field of liver immunology is hampered by practical and technical difficulties.…”

Section: Introductionmentioning

confidence: 99%

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Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

Boeijen

Oord

Hou

et al. 2018

Journal of Leukocyte Biology

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In this study, we describe a method to reliably characterize intrahepatic leukocyte populations using flow cytometry and next‐generation RNA sequencing on fresh human liver biopsies. Over the last decades, immune responses of viral hepatitis patients, and of other liver diseases, have been incompletely characterized. Most studies include peripheral blood samples only, foregoing the possibility to investigate the site of inflammation directly. Here, we show that with an optimized protocol that combines cell sorting and RNA sequencing, we can perform a side by side comparison of both intrahepatic and peripheral immune cells. Using core liver biopsies from chronic hepatitis B virus patients, we show that the expression levels of IFN‐stimulated genes and leukocyte‐specific genes are markedly different in the liver compartment as compared to the peripheral blood. These observations emphasize the need to sample the liver directly. The variation of gene expression profiles in these chronic hepatitis B patients was considerable, despite the uniform treatment with nucleotide analogs and absence of liver inflammation in these patients. Finally, we show that this method can provide a detailed characterization of previously undetected liver‐specific effects of novel candidate therapeutic compounds.

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Section: Resultssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

Boeijen

Oord

Hou

et al. 2018

Journal of Leukocyte Biology

Self Cite

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“…27,76 Such findings have also been confirmed in the intrahepatic compartment, where viral suppression resulted in limited changes in NK cell function. 78 However, during early NA treatment, in patients with raised transaminases, LdT demonstrated an expansion of CD56 bright NK cells via upregulation of IL-15 and NKG2D, which may be important in viral control 79 ; however, larger studies are required to evaluate NK cell phenotype and function along with KIR genotyping. NAs have been shown to improve T cell function, although the data regarding nonconventional T cells are sparse.…”

Section: Nucleos(t)ide Analoguesmentioning

confidence: 99%

The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics

Gill

Kennedy

2018

Journal of Viral Hepatitis

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Summary Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussed.

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“…There are no robust and convincing data showing that the number of CD14 + monocytes, resident KCs, pDC (BDCA2 + cells), mDC-BDCA3 + , and NK/NKT cells within the infected liver, or in the peripheral blood, is affected by HBV throughout the natural history of infection [35,65,66,67,68,69]. …”

Section: Interplay Between Hbv and Innate Immunity: Basic Insightsmentioning

confidence: 99%

Interplay between the Hepatitis B Virus and Innate Immunity: From an Understanding to the Development of Therapeutic Concepts

Faure-Dupuy

Lucifora

Durantel

2017

Viruses

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The hepatitis B virus (HBV) infects hepatocytes, which are the main cell type composing a human liver. However, the liver is enriched with immune cells, particularly innate cells (e.g., myeloid cells, natural killer and natural killer T-cells (NK/NKT), dendritic cells (DCs)), in resting condition. Hence, the study of the interaction between HBV and innate immune cells is instrumental to: (1) better understand the conditions of establishment and maintenance of HBV infections in this secondary lymphoid organ; (2) define the role of these innate immune cells in treatment failure and pathogenesis; and (3) design novel immune-therapeutic concepts based on the activation/restoration of innate cell functions and/or innate effectors. This review will summarize and discuss the current knowledge we have on this interplay between HBV and liver innate immunity.

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Similar frequencies, phenotype and activation status of intrahepatic NK cells in chronic HBV patients after long-term treatment with tenofovir disoproxil fumarate (TDF)

Cited by 17 publications

References 17 publications

Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver

The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics

Interplay between the Hepatitis B Virus and Innate Immunity: From an Understanding to the Development of Therapeutic Concepts

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