Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection

Jun Hou, Willem P. Brouwer, Kim Kreefft, Lucio Gama, Sarah L. Price, Harry L.A. Janssen, Pim J. French, Thomas Vanwolleghem, Andre Boonstra

Research output: Contribution to journalArticle

Abstract

Chronic hepatitis B is a highly heterogeneous liver disease characterized by phases with fluctuations in viral replication and progressive liver damage in some, but not all infected individuals. Despite four decades of research, insight into host determinants underlying these distinct clinical phases-immunotolerant, immune active, inactive carrier, and HBeAg-negative hepatitis±remains elusive. We performed an in-depth transcriptome analysis of archived FFPE liver biopsies of each clinical phase to address host determinants associated with the natural history. Therefore, we determined, for the first time, intrahepatic global expression profiles of well-characterized chronic HBV patients at different clinical phases. Our data, obtained by microarray, demonstrate that B cells and NK/cytotoxicrelated genes in the liver, including CD19, TNFRSF13C, GZMH, and KIR2DS3, were differentially expressed across the clinical HBV phases, which was confirmed by modular analysis and also Nanostring arrays in an independent cohort. Compared to the immunotolerant phase, 92 genes were differentially expressed in the liver during the immune active phase, 46 in the inactive carrier phase, and 71 in the HBeAg-negative phase. Furthermore, our study also revealed distinctive transcription of genes associated with cell cycle activity, NF-κB signaling, cytotoxic function and mitochondrial respiration between clinical phases. Our data define for the first time using microarray unique transcriptomes in the HBV-infected liver during consecutive clinical phases. We demonstrate that fluctuations of viral loads and liver damage coincide with fluctuations in the liver transcriptome and point to functionalimmune and non-immune-components contributing to the clinical phenotype in patients.

Original languageEnglish (US)
Article number0179920
JournalPLoS One
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

transcriptomics
Liver
liver
Infection
infection
Hepatitis B e Antigens
Genes
Transcriptome
transcriptome
Microarrays
chronic hepatitis B
Cells
genes
Chronic Hepatitis B
Gene Expression Profiling
liver diseases
virus replication
viral load
Biopsy
Natural History

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hou, J., Brouwer, W. P., Kreefft, K., Gama, L., Price, S. L., Janssen, H. L. A., ... Boonstra, A. (2017). Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection. PLoS One, 12(6), [0179920]. https://doi.org/10.1371/journal.pone.0179920

Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection. / Hou, Jun; Brouwer, Willem P.; Kreefft, Kim; Gama, Lucio; Price, Sarah L.; Janssen, Harry L.A.; French, Pim J.; Vanwolleghem, Thomas; Boonstra, Andre.

In: PLoS One, Vol. 12, No. 6, 0179920, 01.06.2017.

Research output: Contribution to journalArticle

Hou, J, Brouwer, WP, Kreefft, K, Gama, L, Price, SL, Janssen, HLA, French, PJ, Vanwolleghem, T & Boonstra, A 2017, 'Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection', PLoS One, vol. 12, no. 6, 0179920. https://doi.org/10.1371/journal.pone.0179920
Hou, Jun ; Brouwer, Willem P. ; Kreefft, Kim ; Gama, Lucio ; Price, Sarah L. ; Janssen, Harry L.A. ; French, Pim J. ; Vanwolleghem, Thomas ; Boonstra, Andre. / Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection. In: PLoS One. 2017 ; Vol. 12, No. 6.
@article{a1e005ef7f714334baeb6dc0839445e9,
title = "Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection",
abstract = "Chronic hepatitis B is a highly heterogeneous liver disease characterized by phases with fluctuations in viral replication and progressive liver damage in some, but not all infected individuals. Despite four decades of research, insight into host determinants underlying these distinct clinical phases-immunotolerant, immune active, inactive carrier, and HBeAg-negative hepatitis±remains elusive. We performed an in-depth transcriptome analysis of archived FFPE liver biopsies of each clinical phase to address host determinants associated with the natural history. Therefore, we determined, for the first time, intrahepatic global expression profiles of well-characterized chronic HBV patients at different clinical phases. Our data, obtained by microarray, demonstrate that B cells and NK/cytotoxicrelated genes in the liver, including CD19, TNFRSF13C, GZMH, and KIR2DS3, were differentially expressed across the clinical HBV phases, which was confirmed by modular analysis and also Nanostring arrays in an independent cohort. Compared to the immunotolerant phase, 92 genes were differentially expressed in the liver during the immune active phase, 46 in the inactive carrier phase, and 71 in the HBeAg-negative phase. Furthermore, our study also revealed distinctive transcription of genes associated with cell cycle activity, NF-κB signaling, cytotoxic function and mitochondrial respiration between clinical phases. Our data define for the first time using microarray unique transcriptomes in the HBV-infected liver during consecutive clinical phases. We demonstrate that fluctuations of viral loads and liver damage coincide with fluctuations in the liver transcriptome and point to functionalimmune and non-immune-components contributing to the clinical phenotype in patients.",
author = "Jun Hou and Brouwer, {Willem P.} and Kim Kreefft and Lucio Gama and Price, {Sarah L.} and Janssen, {Harry L.A.} and French, {Pim J.} and Thomas Vanwolleghem and Andre Boonstra",
year = "2017",
month = "6",
day = "1",
doi = "10.1371/journal.pone.0179920",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Unique intrahepatic transcriptomics profiles discriminate the clinical phases of a chronic HBV infection

AU - Hou, Jun

AU - Brouwer, Willem P.

AU - Kreefft, Kim

AU - Gama, Lucio

AU - Price, Sarah L.

AU - Janssen, Harry L.A.

AU - French, Pim J.

AU - Vanwolleghem, Thomas

AU - Boonstra, Andre

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Chronic hepatitis B is a highly heterogeneous liver disease characterized by phases with fluctuations in viral replication and progressive liver damage in some, but not all infected individuals. Despite four decades of research, insight into host determinants underlying these distinct clinical phases-immunotolerant, immune active, inactive carrier, and HBeAg-negative hepatitis±remains elusive. We performed an in-depth transcriptome analysis of archived FFPE liver biopsies of each clinical phase to address host determinants associated with the natural history. Therefore, we determined, for the first time, intrahepatic global expression profiles of well-characterized chronic HBV patients at different clinical phases. Our data, obtained by microarray, demonstrate that B cells and NK/cytotoxicrelated genes in the liver, including CD19, TNFRSF13C, GZMH, and KIR2DS3, were differentially expressed across the clinical HBV phases, which was confirmed by modular analysis and also Nanostring arrays in an independent cohort. Compared to the immunotolerant phase, 92 genes were differentially expressed in the liver during the immune active phase, 46 in the inactive carrier phase, and 71 in the HBeAg-negative phase. Furthermore, our study also revealed distinctive transcription of genes associated with cell cycle activity, NF-κB signaling, cytotoxic function and mitochondrial respiration between clinical phases. Our data define for the first time using microarray unique transcriptomes in the HBV-infected liver during consecutive clinical phases. We demonstrate that fluctuations of viral loads and liver damage coincide with fluctuations in the liver transcriptome and point to functionalimmune and non-immune-components contributing to the clinical phenotype in patients.

AB - Chronic hepatitis B is a highly heterogeneous liver disease characterized by phases with fluctuations in viral replication and progressive liver damage in some, but not all infected individuals. Despite four decades of research, insight into host determinants underlying these distinct clinical phases-immunotolerant, immune active, inactive carrier, and HBeAg-negative hepatitis±remains elusive. We performed an in-depth transcriptome analysis of archived FFPE liver biopsies of each clinical phase to address host determinants associated with the natural history. Therefore, we determined, for the first time, intrahepatic global expression profiles of well-characterized chronic HBV patients at different clinical phases. Our data, obtained by microarray, demonstrate that B cells and NK/cytotoxicrelated genes in the liver, including CD19, TNFRSF13C, GZMH, and KIR2DS3, were differentially expressed across the clinical HBV phases, which was confirmed by modular analysis and also Nanostring arrays in an independent cohort. Compared to the immunotolerant phase, 92 genes were differentially expressed in the liver during the immune active phase, 46 in the inactive carrier phase, and 71 in the HBeAg-negative phase. Furthermore, our study also revealed distinctive transcription of genes associated with cell cycle activity, NF-κB signaling, cytotoxic function and mitochondrial respiration between clinical phases. Our data define for the first time using microarray unique transcriptomes in the HBV-infected liver during consecutive clinical phases. We demonstrate that fluctuations of viral loads and liver damage coincide with fluctuations in the liver transcriptome and point to functionalimmune and non-immune-components contributing to the clinical phenotype in patients.

UR - http://www.scopus.com/inward/record.url?scp=85021684628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021684628&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0179920

DO - 10.1371/journal.pone.0179920

M3 - Article

C2 - 28662087

AN - SCOPUS:85021684628

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - 0179920

ER -