Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE230397 | GEO | 2023/04/28
REPOSITORIES: GEO
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Project description:Since little information is available on the processes in the liver associated with the natural history during chronic HBV infections, we now examined hepatic transcriptomes to identify distinctive gene expression profiles in the HBV clinical phases. We show that the transcriptomes of mild fibrotic, HBV-infected livers were significantly different from those with comorbidities. Across the clinical HBV phases, comparable intrahepatic ISG expression was observed. However, global transcription was most distinctive between the immunotolerant and the immunoactive phases (n=92 genes), followed by the immunotolerant and the HBeAg-negative hepatitis phase (n=71 genes), and the immunotolerant and the inactive carrier phase (n=46 genes). Among these were CD19, TNFRSF13C, granzyme H, and KIR2DS3. Moreover, during these clinical phases, 4 intrinsic functional clusters (IFC) with distinctive transcriptional activity were identified by combined global module analysis. These discriminative clusters contained B-cell and cell cycle-related genes, which were highly expressed in liver during the immunoactive phase; and NK-cell and mitochondria respiration-related genes in the HBeAg-negative hepatitis phase. Our data define distinctive transcriptomes in the liver during HBV clinical phases. We observed important differences between the liver and blood in transcription levels of ISG and cell cycle genes, but, strikingly, also a high degree of overlap in expression patterns of B- and NK-cell genes during the immune active phases.
2017-06-10 | GSE83898 | GEO
Project description:Background: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection—immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases—remains unexplored. </p> Methods: To investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels. </p> Results: Our data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate–NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase. </p> Conclusions: The work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate–NADH shuttle. </p> The Lipid assays and the Biogenic amine and Acyl-carnitine assays for this study can be found in the MetaboLights studies MTBLS279 and MTBLS280 respectively.
2016-06-06 | MTBLS253 | MetaboLights
Project description:Background: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection—immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases—remains unexplored. </p> Methods: To investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels. </p> Results: Our data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate–NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase. </p> Conclusions: The work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate–NADH shuttle. </p> The Oxylipin assay and the Lipid assays for this study can be found in the MetaboLights studies MTBLS253 and MTBLS279 respectively.
2016-06-06 | MTBLS280 | MetaboLights
Project description:Background: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection—immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases—remains unexplored. </p> Methods: To investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels. </p> Results: Our data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate–NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase. </p> Conclusions: The work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate–NADH shuttle. </p> The Oxylipin assay and the Biogenic amine and Acyl-carnitine assays for this study can be found in the MetaboLights studies MTBLS253 and MTBLS280 respectively.
2016-06-06 | MTBLS279 | MetaboLights
Project description:This study was conducted to assess how long-term nucleoside analogue (NUC) treatment and HBeAg loss alters the transcriptome of blood mononuclear cells from chronic HBV patients
2020-11-01 | GSE159413 | GEO
Project description:Previous studies have paid more attention to hepatitis B e antigen (HBeAg) intrauterine exposure, however the effect of solely hepatitis B surface antigen (HBsAg) exposure on the immune response of offspring against hepatitis B virus (HBV) is still unclear. In this study, we investigated whether HBsAg intrauterine exposure affected the offspring's immune response against HBV and the relevant mechanism, which is important for the prevention of HBV mother-to-infant transmission.
2021-12-01 | GSE162718 | GEO
Project description:The HBeAg is a well-documented risk factor for HCC in epidemiological studies. The biological role of HBeAg in HBV-related HCC remains poorly understood. The HBeAg-mediated differential expression of host miRNAs We used miRNA microarray chips to assess the host cellular miRNA expression profile in response to HBeAg expression in Huh7 cells
2017-07-01 | GSE90146 | GEO
Project description:The presence of HBeAg has been linked to an increased risk of HBV-realted HCC. However, the biological role of HBeAg in modulating host gene expression is poorly understood. Therefore, we performed a cDNA microarray in response to presence of HBeAg in Huh-7 cells. We used human primeview gene expression microarray chips to assess the host cellular mRNA expression profile in response to HBeAg in Huh7 cells
2017-07-01 | GSE90115 | GEO
Project description:PolyA-RNA sequencing on Peripheral Blood Mononuclear Cells in patients infected with HIV and healthy donnors. Patients were effectively treated with cART (virological controlled and CD4+ T-cell counts over 500) for an extended period. HIV infected patients were not coinfected with HCV or HBV.
2020-05-31 | E-MTAB-8249 | biostudies-arrayexpress
Project description:The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host and highlight the plasticity of the fetal immune system following viral exposure in utero. RNA was extracted from 15 cord blood samples comprising of healthy cord blood monocytes (n=4), HBV-exposed cord blood monocytes (n=3), healthy cord blood plasmacytoid dendritic cells (n=4), and HBV-exposed cord blood plasmacytoid dendritic cells (n=4). Healthy adult peripheral blood monocytes (n=3) were included for comparison. The immune profile was analyzed using Nanostring and nCounter® GX Human Immunology Kit v1, comprising probes for a total of 511 immune genes.
2015-06-30 | E-GEOD-65389 | biostudies-arrayexpress