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.
Subject(s)
Fatty Liver, Alcoholic/metabolism , Transcriptome , Adult , Cell Proliferation , Ethnicity , Fatty Liver, Alcoholic/drug therapy , Fatty Liver, Alcoholic/ethnology , Fatty Liver, Alcoholic/genetics , Female , Glucocorticoids/therapeutic use , Hepatocytes/metabolism , Hepatocytes/physiology , Humans , Male , Middle Aged , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolismABSTRACT
Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. More than half of these cases are attributable to gastrointestinal malignancies including gastric, colonic, and pancreatic cancer. In addition, gynecologic (ovarian, uterine cancer), unknown primary tumors, and, rarely, bladder or respiratory malignancies may cause umbilical metastasis. We report the case of a Sister Mary Joseph nodule originating from a hilar cholangiocarcinoma. Umbilical nodules should prompt clinical evaluation, as these tumors are usually associated with poor prognosis.
