Differential hepatic gene expression profiles identify improvement in MELD score following decompensation in alcoholic liver disease
(2012) AASLD Annual meeting — Location: Boston (9.November.2012)
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- Abstract
- We aimed to study the hepatic differentially expressed genes associated with 1) bone marrow stem cell therapy (BMST) and 2) the evolution of liver function during follow-up in a well-characterized patients’ population of acutely decompensated alcoholic liver disease (ALD). Methods: This study derives from the material and bio-clinical data issued from a trial of autologous bone marrow stem cell transplantation in patients with ALD (Hepatology 2011, A62), for which an informed consent was obtained in all cases. Transcriptome profiling was performed on snap liver frozen samples with Affymetrix GeneChip Human arrays containing 43134 transcripts. Differential gene expression was analyzed on liver tissue obtained at the 4-week follow-up visit after BMST (n=12) or after standard medical therapy alone (n=12). We also compared differentially expressed transcripts on baseline biopsy performed early after admission, according to the evolution of liver insufficiency at 3 months, irrespective of treatment allocation. We defined patients with a ≥ 3 points decrease in MELD compared to baseline value as “improvers” (n=17), and those with less than 3 points decrease in MELD as “non improvers” (n=13). Serum soluble receptor of TNF (STNF) and hepatocyte growth factor (HGF) were measured. Results: 1) Autologous BMST did not provide any clinical, biological or histological benefits compared to standard medical therapy (Hepatology 2011, A62). However, in stem cell treated patients, at a 5% false discovery rate, gene expression changes at 4 weeks of follow-up were predominantly associated with inflammation and immune chemotaxis (SAA, CXCL6, CXCL13, CCL19), as well as in hematopoietic cell protein (CD45), compared to patients with standard therapy alone. 2) Differentially expressed genes in baseline biopsy characterized the “improvers” and the “non-improvers”. Genes involved in cell cycle mitosis (cyclin A and B, CDK1, CDC20) were upregulated in improvers compared to non-improvers, as well as genes involved in monocyte attraction, cytoskeleton motility and Wnt signaling (CXCL14, actin, collagen, CD68, Wnt11). Both serum STNF and HGF were also higher in improvers compared to non-improvers. Conclusion: In patients with decompensated ALD, the effect of BMST on liver tissue at 4 weeks of follow-up is limited to changes in genes linked with lympho-monocyte chemotaxis and one hematopoietic cell surface protein. The differentially expressed genes involved in cell proliferation at admission are associated with the clinical outcome, supporting the role of liver cell regeneration in the improvement of liver function.
- Affiliations
Hôpitaux Universitaires de Genève Service de Gastro-entérologie et Hépatologie
Citations
Lanthier, N., Rubbia-Brandt, L., Kindler, V., Hadengue, A., & Spahr, L. (2012). Differential hepatic gene expression profiles identify improvement in MELD score following decompensation in alcoholic liver disease. Hepatology, 56(S1), 982A. https://hdl.handle.net/2078.5/201491 (Original work published 2012)