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

Abstract

OBJECTIVES:

Inflammatory activation of resident hepatic macrophages (Kupffer cells) by portal-derived lipopolysaccharide (LPS) has a primary role in animal models of alcoholic liver disease, but it has not been systematically or longitudinally studied in human alcoholic hepatitis (AH).

METHODS:

We followed 50 patients with AH for 30 days. 26 patients with stable alcoholic cirrhosis and 20 healthy individuals were controls. We measured the plasma (P) concentrations of soluble CD163 (sCD163; a specific marker of inflammatory macrophage activation) and the expression of CD163 in liver tissue by immunohistochemistry and stereology of liver biopsies. We also measured the key components of the LPS pathway, P-LPS, sCD14, and LPS-binding protein (LBP), by enzyme-linked immunosorbent assay (ELISA). The 84-day mortality was registered.

RESULTS:

At study entry, the sCD163 concentration was 10-fold higher than in the healthy controls and 30% higher than in the stable cirrhotics (P<0.002), and it correlated with the Glasgow Alcoholic Hepatitis, Model for End-stage Liver Disease, and Child-Pugh scores (r>0.35, P<0.02, all). The liver biopsies confirmed markedly increased CD163 staining (P<0.01). P-LPS, P-CD14, and P-LBP were increased to the same degree as sCD163. During the follow-up, the sCD163 and LPS pathway components all decreased by ∼25% (P<0.05) but remained higher than in both control groups. sCD163 was an independent predictor of the 84-day mortality.

CONCLUSIONS:

The hepatic inflammation of human AH involves marked activation of hepatic macrophages, likely via the LPS pathway. Hepatic macrophages may thus present a target for biological therapy of AH.

• Authors: Thomas Damgaard Sandahl, Henning Grønbaek, Holger Jon Møller, Sidsel Støy, Karen Luise Thomsen, Anders Kirch Dige, Jørgen Agnholt, Stephen Hamilton-Dutoit, Steffen Thiel, Hendrik Vilstrup
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 109 Issue 11 Pg. 1749-56 (Nov 2014) ISSN: 1572-0241 [Electronic] United States
• PMID: 25155228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD163 antigen
• Lipopolysaccharides
• Receptors, Cell Surface

Topics

• Antigens, CD (immunology)
• Antigens, Differentiation, Myelomonocytic (immunology)
• Biopsy
• Case-Control Studies
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Hepatitis, Alcoholic (immunology)
• Humans
• Immunohistochemistry
• Lipopolysaccharides (immunology)
• Macrophage Activation
• Male
• Middle Aged
• Prospective Studies
• Receptors, Cell Surface (immunology)