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

作者：Shvetank Sharma, Jaswinder Singh Maras, Sukanta Das, Shabir Hussain, Ashwani Kumar Mishra, Saggere Muralikrishna Shasthry, Chhagan Bihari Sharma, Emmanuel Weiss, Laure Elkrief, Pierre‐Emmanuel Rautou, Hélène Gilgenkrantz, Sophie Lotersztajn, Valérie Paradis, Pierre de la Grange, Christophe Junot, Richard Moreau, Shiv Kumar Sarin · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/s41598-017-07161-4 · 被引用次数：23 · 研究领域：Alcohol Consumption and Health Effects、Liver Disease Diagnosis and Treatment、Eicosanoids and Hypertension Pharmacology

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.