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Hepatic macrophage activation and the LPS pathway in patients with alcoholic hepatitis: a prospective cohort study

Thomas Damgaard Sandahl1, Henning Grønbaek1, Holger Jon Møller2

  • 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

The American Journal of Gastroenterology
|August 27, 2014
PubMed
Abstract

Insights

In human alcoholic hepatitis (AH), hepatic macrophages show significant inflammatory activation, likely driven by lipopolysaccharide (LPS). This macrophage activation is a predictor of mortality and a potential therapeutic target.

Area of Science:

  • Hepatology
  • Immunology
  • Gastroenterology

Background:

  • Inflammatory activation of Kupffer cells by lipopolysaccharide (LPS) is crucial in animal models of alcoholic liver disease.
  • This process has not been systematically studied in human alcoholic hepatitis (AH).

Purpose of the Study:

  • To investigate the longitudinal changes in hepatic macrophage activation and LPS pathway components in patients with AH.
  • To assess the correlation of these markers with disease severity and mortality.

Main Methods:

  • Longitudinal study of 50 AH patients over 30 days, with controls including 26 stable cirrhotics and 20 healthy individuals.
  • Measurement of plasma soluble CD163 (sCD163), liver CD163 expression, plasma LPS, sCD14, and LPS-binding protein (LBP).
  • Correlation analysis with clinical scores (Glasgow AH, MELD, Child-Pugh) and 84-day mortality.

Main Results:

  • Patients with AH exhibited significantly elevated sCD163 and LPS pathway markers compared to controls.
  • sCD163 levels correlated with AH severity scores.
  • Markers decreased during follow-up but remained elevated; sCD163 independently predicted 84-day mortality.

Conclusions:

  • Human AH involves significant hepatic macrophage activation, likely mediated by the LPS pathway.
  • Hepatic macrophages represent a potential therapeutic target for biological treatment of AH.

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