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Sci Rep. 2017 Jul 28;7(1):6816. doi: 10.1038/s41598-017-07161-4.

Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness.

Author information

1
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
2
NexGenBio Life Sciences, New Delhi, India.
3
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
4
Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India.
5
INSERM, Université Paris Diderot, CNRS, Centre de Recherche sur l'Inflammation (CRI), Paris, France.
6
Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
7
INSERM, Université Paris Descartes, CNRS, Institut Cochin, Paris, France.
8
Département de D'Anatomopathologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
9
Genosplice, Institut du Cerveau et de la Moelle épinière ICM, Paris, France.
10
Laboratoire d'Etude du Métabolisme des Médicaments, DSV/iBiTec-S/SPI, CEA-Saclay, MetaboHUB-Paris, Paris, France.
11
Laboratoire d'Excellence Inflamex, COMUE Sorbonne Paris Cité, Paris, France.
12
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. sksarin@ilbs.in.

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.

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