Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness
Abstract Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene express...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07161-4 |
| _version_ | 1818420141478641664 |
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| author | Shvetank Sharma Jaswinder S. Maras Sukanta Das Shabir Hussain Ashwani K. Mishra Saggere M. Shasthry Chhagan B. Sharma Emmanuel Weiss Laure Elkrief Pierre-Emmanuel Rautou Hélène Gilgenkrantz Sophie Lotersztajn Valérie Paradis Pierre de la Grange Christophe Junot Richard Moreau Shiv K. Sarin |
| author_facet | Shvetank Sharma Jaswinder S. Maras Sukanta Das Shabir Hussain Ashwani K. Mishra Saggere M. Shasthry Chhagan B. Sharma Emmanuel Weiss Laure Elkrief Pierre-Emmanuel Rautou Hélène Gilgenkrantz Sophie Lotersztajn Valérie Paradis Pierre de la Grange Christophe Junot Richard Moreau Shiv K. Sarin |
| author_sort | Shvetank Sharma |
| collection | DOAJ |
| description | Abstract Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR. |
| first_indexed | 2024-12-14T12:49:45Z |
| format | Article |
| id | doaj.art-72ec0795f3c643bab6aa78a674e6170a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T12:49:45Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-72ec0795f3c643bab6aa78a674e6170a2022-12-21T23:00:42ZengNature PortfolioScientific Reports2045-23222017-07-01711910.1038/s41598-017-07161-4Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsivenessShvetank Sharma0Jaswinder S. Maras1Sukanta Das2Shabir Hussain3Ashwani K. Mishra4Saggere M. Shasthry5Chhagan B. Sharma6Emmanuel Weiss7Laure Elkrief8Pierre-Emmanuel Rautou9Hélène Gilgenkrantz10Sophie Lotersztajn11Valérie Paradis12Pierre de la Grange13Christophe Junot14Richard Moreau15Shiv K. Sarin16Department of Molecular and Cellular Medicine, Institute of Liver and Biliary SciencesDepartment of Molecular and Cellular Medicine, Institute of Liver and Biliary SciencesDepartment of Molecular and Cellular Medicine, Institute of Liver and Biliary SciencesDepartment of Molecular and Cellular Medicine, Institute of Liver and Biliary SciencesNexGenBio Life SciencesDepartment of Hepatology, Institute of Liver and Biliary SciencesDepartment of Pathology, Institute of Liver and Biliary SciencesINSERM, Université Paris Diderot, CNRS, Centre de Recherche sur l’Inflammation (CRI)Département Hospitalo-Universitaire (DHU) UNITY, Service d’Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de ParisDépartement Hospitalo-Universitaire (DHU) UNITY, Service d’Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de ParisINSERM, Université Paris Descartes, CNRS, Institut CochinINSERM, Université Paris Diderot, CNRS, Centre de Recherche sur l’Inflammation (CRI)INSERM, Université Paris Diderot, CNRS, Centre de Recherche sur l’Inflammation (CRI)Genosplice, Institut du Cerveau et de la Moelle épinière ICMLaboratoire d’Etude du Métabolisme des Médicaments, DSV/iBiTec-S/SPI, CEA-Saclay, MetaboHUB-ParisINSERM, Université Paris Diderot, CNRS, Centre de Recherche sur l’Inflammation (CRI)Department of Hepatology, Institute of Liver and Biliary SciencesAbstract Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.https://doi.org/10.1038/s41598-017-07161-4 |
| spellingShingle | Shvetank Sharma Jaswinder S. Maras Sukanta Das Shabir Hussain Ashwani K. Mishra Saggere M. Shasthry Chhagan B. Sharma Emmanuel Weiss Laure Elkrief Pierre-Emmanuel Rautou Hélène Gilgenkrantz Sophie Lotersztajn Valérie Paradis Pierre de la Grange Christophe Junot Richard Moreau Shiv K. Sarin Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness Scientific Reports |
| title | Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness |
| title_full | Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness |
| title_fullStr | Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness |
| title_full_unstemmed | Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness |
| title_short | Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness |
| title_sort | pre therapy liver transcriptome landscape in indian and french patients with severe alcoholic hepatitis and steroid responsiveness |
| url | https://doi.org/10.1038/s41598-017-07161-4 |
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