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PLoS One. 2018 Sep 5;13(9):e0203200. doi: 10.1371/journal.pone.0203200. eCollection 2018.

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.

Author information

1
Gastro Unit, Medical Division, Copenhagen University Hospital Amager Hvidovre, Hvidovre, Denmark.
2
Centre of Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
3
Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
4
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
5
Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Abstract

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.

Conflict of interest statement

NK and FB received study medication and placebo free of charge from Norgine for the clinical trial. Norgine had no further engagement in trial design, conduction of the trial or analysis of trial data. FB received speaker honorarium from Norgine. JSP and SM declare no conflicts of interest. HG received funding from the NOVO Nordisk Foundation, Abbvie, Intercept, and ‘Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat’ and is on advisory board of IPSEN and Novartis. HJM received funding from the Danish Strategic Research Council (10-092797). MAK, DJL, NSG and MJN are full time employees at Nordic Bioscience and MAK and DJL own stock in Nordic Bioscience. NK, FB, JSP, SM, HG and HJM have no financial interests in Nordic Bioscience. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

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