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

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

doi:10.1371/journal.pone.0203200

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

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

Department of Clinical Medicine

5 Citations (Scopus)

32 Downloads (Pure)

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.

Original language	English
Article number	e0203200
Journal	PLoS ONE
Volume	13
Issue number	9
Number of pages	12
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0203200
Publication status	Published - Sept 2018

Keywords

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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Kimer, N., Gudmann, N. S., Pedersen, J. S., Møller, S., Nielsen, M. J., Leeming, D. J., Karsdal, M. A., Møller, H. J., Bendtsen, F., & Grønbæk, H. (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. PLoS ONE, 13(9), [e0203200]. https://doi.org/10.1371/journal.pone.0203200

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 et al.

In: PLoS ONE, Vol. 13, No. 9, e0203200, 09.2018.

Research output: Contribution to journal › Journal article › Research › peer-review

Kimer, N, Gudmann, NS, Pedersen, JS, Møller, S, Nielsen, MJ, Leeming, DJ, Karsdal, MA, Møller, HJ, Bendtsen, F & Grønbæk, H 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', PLoS ONE, vol. 13, no. 9, e0203200. https://doi.org/10.1371/journal.pone.0203200

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title = "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",

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.",

keywords = "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",

author = "Nina Kimer and Gudmann, {Natasja St{\ae}hr} and Pedersen, {Julie Steen} and S{\o}ren M{\o}ller and Nielsen, {Mette Juul} and Leeming, {Diana Julie} and Karsdal, {Morten Asser} and M{\o}ller, {Holger Jon} and Flemming Bendtsen and Henning Gr{\o}nb{\ae}k",

year = "2018",

month = sep,

doi = "10.1371/journal.pone.0203200",

language = "English",

volume = "13",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

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 - 2018/9

Y1 - 2018/9

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

SN - 1932-6203

VL - 13

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 9

M1 - e0203200

ER -

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

Abstract

Keywords

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