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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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. / Kimer, Nina; Gudmann, Natasja Stæhr; Pedersen, Julie Steen; Møller, Søren; Nielsen, Mette Juul; Leeming, Diana Julie; Karsdal, Morten Asser; Møller, Holger Jon; Bendtsen, Flemming; Grønbæk, Henning.
I: PLoS ONE, Bind 13, Nr. 9, e0203200, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis
T2 - Results from a randomized, placebo controlled trial
AU - Kimer, Nina
AU - Gudmann, Natasja Stæhr
AU - Pedersen, Julie Steen
AU - Møller, Søren
AU - Nielsen, Mette Juul
AU - Leeming, Diana Julie
AU - Karsdal, Morten Asser
AU - Møller, Holger Jon
AU - Bendtsen, Flemming
AU - Grønbæk, Henning
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Antigens, CD/blood
KW - Antigens, Differentiation, Myelomonocytic/blood
KW - Biomarkers/blood
KW - Collagen Type III/blood
KW - Collagen Type IV/blood
KW - Double-Blind Method
KW - Female
KW - Gastrointestinal Agents/therapeutic use
KW - Humans
KW - Lectins, C-Type/blood
KW - Liver Cirrhosis/blood
KW - Male
KW - Mannose-Binding Lectins/blood
KW - Middle Aged
KW - Receptors, Cell Surface/blood
KW - Rifaximin/therapeutic use
KW - Severity of Illness Index
KW - Treatment Outcome
U2 - 10.1371/journal.pone.0203200
DO - 10.1371/journal.pone.0203200
M3 - Journal article
C2 - 30183743
VL - 13
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e0203200
ER -
ID: 216568658