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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

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

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. More... »

PAGES

6816

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-07161-4

DOI

http://dx.doi.org/10.1038/s41598-017-07161-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090882991

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28754919


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