Proliferative activity in CK7 positive cells and hepatocytes as well as macrophage expansion predict MELD score improvement in decompensated alcoholic liver disease (ALD)

Lanthier, Nicolas;Rubbia-Brandt, Laura;Frossard, Jean-Louis;Hadengue, Antoine;Spahr, Laurent
(2012) Annual Meeting of the Swiss Society of Gastroenterology — Location: Interlaken (20.September.2012)

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Authors
  • Lanthier, Nicolasorcid-logoUCLouvain
    Author
  • Rubbia-Brandt, LauraHôpitaux Universitaires de Genève
    Collaborator
  • Frossard, Jean-LouisHôpitaux Universitaires de Genève
    Collaborator
  • Hadengue, AntoineHôpitaux Universitaires de Genève
    Author
  • Spahr, LaurentHôpitaux Universitaires de Genève
    Author
Abstract
Background: Liver regeneration plays a key role in the prognosis of acute-on-chronic ALD. Both hepatic progenitor cell (HPC) and liver macrophages increase in response to acute liver injury, but the prognostic significance of these changes remains to be determined. We studied the expansion of both macrophage and proliferative HPC compartments on liver biopsies obtained from the bone marrow stem cell trial in ALD, and correlated with the outcome at 3 months. Methods: 58 patients with decompensated ALD (MELD 19) were included. Proliferative HPC were analyzed (immunohistochemistry) on liver biopsy performed at admission, by manual count of Ki67+/CK7+ and CK7-cells. Macrophage expansion was determined by CD68+ morphometric analysis. Cytokines and markers of regeneration were measured by immunoassays on serum and quantitative PCR on liver tissue. A ≥ 3 points decrease in MELD at 3 months defined the responders. Results Responders Non responders CK7+/Ki67+ cells (HPC) 1.9±1.5 0.9±0.9 0.01 CK7-/Ki67+ cells (mature hepatocytes) 4.1±3.6 1.8±1.4 0.01 Liver macrophages (% of surface area) 4.4% 3.3% 0.05 Both hepatocyte growth factor and soluble TNF receptor serum levels were higher in responders. Liver PCR analysis showed that liver macrophagic expansion was associated with an increase in TWEAK receptor mRNA expression (p<0.05), known to stimulate HPC proliferation. Conclusion: This is the first study showing that markers of liver cell proliferation obtained on baseline liver biopsy predicts the clinical outcome at 3 months in patients with decompensated ALD. These data support the role of liver biopsy not only for diagnostic purposes but also to determine the short term prognosis.
Affiliations
  • Hôpitaux Universitaires de GenèveService de Gastro-entérologie et Hépatologie

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Lanthier, N., Hadengue, A., & Spahr, L. (2012). Proliferative activity in CK7 positive cells and hepatocytes as well as macrophage expansion predict MELD score improvement in decompensated alcoholic liver disease (ALD). Swiss Medical Weekly, 142(Suppl 194), 4S. https://hdl.handle.net/2078.5/201353 (Original work published 2012)