No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized, placebo controlled trial

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Nina Kimer, Natasja Stæhr Gudmann, Julie Steen Pedersen, Søren Møller, Mette Juul Nielsen, Diana Julie Leeming, Morten Asser Karsdal, Holger Jon Møller, Flemming Bendtsen, Henning Grønbæk

BACKGROUND AND AIMS: Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by systemic inflammation induced by bacterial translocation. Therefore, we aimed to investigate the effect of rifaximin-α, an antibiotic with effect on gut bacteria, on sCD163, sMR, and collagen metabolites.

METHODS: Fifty-four clinically stable patients with decompensated cirrhosis were randomized to 4 weeks treatment with rifaximin-α (n = 36) or placebo (n = 18). Macrophage markers sCD163, sMR and markers of collagen fibrogenesis (C3M and C4M) and formation (PRO-C3 and P4NPS7) were analysed in plasma before and after treatment.

RESULTS: sCD163 and sMR levels were associated with liver disease severity (MELD score, sCD163 rho = 0.47, p<0.001 and sMR rho = 0.37, p = 0.005). There was no effect of Rifaximin-α on sCD163 levels (median (range) sCD163 5.64(2.02 to 10.8) at baseline versus 4.42(1.98 to 8.92) at follow-up in the rifaximin-α group and 4.85 (2.29 to 12.1) at baseline versus 4.32 (1.98 to 12.4) at follow-up in the placebo-group), p = 0.34); nor sMR levels, p = 0.34. Also in patients with elevated lipopolysaccharide binding protein (> 5.9 μg/ml, 38 patients) there was no effect of rifaximin-α on sCD163 (p = 0.49) or sMR levels (p = 0.32).

CONCLUSION: We confirmed that macrophage activation markers sCD163 and sMR are directly associated to liver disease severity (MELD score). However, rifaximin-α has no effect on sCD163, sMR or collagen markers in decompensated cirrhosis and does therefore not seem to interfere with macrophage activation or fibrogenesis.

Original languageEnglish
Article numbere0203200
JournalPLoS ONE
Volume13
Issue number9
Number of pages12
ISSN1932-6203
DOIs
Publication statusPublished - 2018

    Research areas

  • Adult, Aged, Antigens, CD/blood, Antigens, Differentiation, Myelomonocytic/blood, Biomarkers/blood, Collagen Type III/blood, Collagen Type IV/blood, Double-Blind Method, Female, Gastrointestinal Agents/therapeutic use, Humans, Lectins, C-Type/blood, Liver Cirrhosis/blood, Male, Mannose-Binding Lectins/blood, Middle Aged, Receptors, Cell Surface/blood, Rifaximin/therapeutic use, Severity of Illness Index, Treatment Outcome

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