Neutralization of lipopolysaccharide effects in liver diseases, the quest for the holy grail

Authors

  • Arnaud Galbois M.D.,

    1. Université Pierre et Marie Curie Université de Paris 6, Unité Mixte de Recherche_S 938, CdR Saint-Antoine, Paris, France
    2. Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 938, CdR Saint-Antoine, Paris, France
    3. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service de Réanimation Médicale, Paris, France
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  • Dominique Thabut M.D., Ph.D.,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 938, CdR Saint-Antoine, Paris, France
    2. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service de Réanimation Médicale, Paris, France
    3. AP-HP, Hôpital la Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
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  • Richard Moreau M.D., Ph.D.,

    1. INSERM, Unité 773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Paris, France
    2. AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France
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  • Didier Lebrec M.D., Ph.D.

    1. INSERM, Unité 773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Paris, France
    2. AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France
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  • Potential conflict of interest: Nothing to report.

To the Editor:

We read with great interest the article in HEPATOLOGY by Nolan on the role of lipopolysaccharide (LPS) in liver injury.1 This review, written by a pioneer of this approach, details the main studies that progressively established gut-derived LPS as a key cofactor in acute and chronic liver disease in the last half-century and more recent studies that tried to prevent LPS-induced damages by reducing or by neutralizing plasma LPS or proinflammatory cytokines. However, we think some important recent studies should have been discussed in this review.

Among the studies exploring possibilities to neutralize LPS, those which assessed the effects high-density lipoprotein (HDL) have not been mentioned.2-4 HDL particles are multifunctional lipoprotein complexes that transport lipids and have several anti-inflammatory properties. In cirrhosis, HDL plasma concentrations are decreased and could impair the host's ability to neutralize LPS.3 In cirrhotic rats with ascites, two recent studies have shown that HDL administration reduced the effects of LPS on tumor necrosis factor-α production2, 4 and systemic hemodynamics, restoring liver endothelial nitric oxide synthase activity and decreasing portal pressure.2 These studies suggest that the excessive proinflammatory response to LPS in cirrhosis may be attributable, at least in part, to reduced LPS neutralization by HDL. Incubation of whole blood with reconstituted HDL prevents LPS-induced tumor necrosis factor-α and interleukin-6 overproduction by monocytes of patients with cirrhosis.3 Therefore, we believe that restoring HDL content in patients with cirrhosis may be a research avenue to follow in the future.

We are conscious that mentioning all the studies related to this crucial subject is very difficult, but we think that the studies we report here are worth being cited in such a review.

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