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Rifaximin-alpha red...
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Patel, Vishal C.Kings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.;Roger Williams Inst Hepatol, Fdn Liver Res, 111 Coldharbour Lane, London SE5 9NT, England.
(författare)
Rifaximin-alpha reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy : RIFSYS randomised controlled trial
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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Elsevier BV,2022
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-309444
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-309444URI
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https://doi.org/10.1016/j.jhep.2021.09.010DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20220304
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Background & Aims: Rifaximin-alpha is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-alpha reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. Methods: In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-alpha (550 mg BID) or placebo for 90 days. Primary outcome: 50% reduction in neutrophil oxidative burst (OB) at 30 days. Secondary outcomes: changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. Results: Patients were well-matched: median MELD (11 rifaximin-alpha vs. 10 placebo). Rifaximin-alpha did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p = 0.48). However, HE grade normalised (p = 0.014) and PHES improved (p = 0.009) after 30 days on rifaximin-alpha. Rifaximin-alpha reduced circulating neutrophil TLR-4 expression on day 30 (p = 0.021) and plasma tumour necrosis factor-alpha (TNF-alpha) (p <0.001). Rifaximin-a suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-alpha promoted a TNF-alpha-and interleukin17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-alpha were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). Conclusion: Rifaximin-alpha led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-alpha plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lee, SunjaeKTH,Science for Life Laboratory, SciLifeLab,Kings Coll London, Inst Dent, Ctr Host Microbiome Interact, London, England.;Gwangju Inst Sci & Technol, Sch Life Sci, Gwangju 61005, South Korea.(Swepub:kth)u15y67rb
(författare)
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McPhail, Mark J. W.Kings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.;Imperial Coll London, Biomol Med, Div Computat & Syst Med, Dept Surg & Canc, London, England.
(författare)
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Da Silva, KevinUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Guilly, SusieUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Zamalloa, AneKings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.
(författare)
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Witherden, ElizabethKings Coll London, Inst Dent, Ctr Host Microbiome Interact, London, England.
(författare)
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Stoy, SidselAarhus Univ Hosp, Dept Gastroenterol & Hepatol, Aarhus, Denmark.
(författare)
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Vijay, Godhev Kumar ManakkatKings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Pons, NicolasUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Galleron, NathalieUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Huang, XaiohongKings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Gencer, SelinImperial Coll London, Biomol Med, Div Computat & Syst Med, Dept Surg & Canc, London, England.
(författare)
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Coen, MuireannImperial Coll London, Biomol Med, Div Computat & Syst Med, Dept Surg & Canc, London, England.
(författare)
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Tranah, Thomas HenryKings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Wendon, Julia AlexisKings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Bruce, Kenneth D.Kings Coll London, Inst Pharmaceut Sci, 5th Floor Franklin Wilkins Bldg, London, England.
(författare)
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Le Chatelier, EmmanuelleUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Ehrlich, Stanislav DuskoUniv Paris Saclay, INRAE, MetaGenoPolis, F-78350 Jouy En Josas, France.
(författare)
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Edwards, Lindsey AnnKings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Shoaie, SaeedKTH,Science for Life Laboratory, SciLifeLab,Kings Coll London, Inst Dent, Ctr Host Microbiome Interact, London, England.(Swepub:kth)u1buycsp
(författare)
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Shawcross, Debbie LindsayKings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.
(författare)
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Kings Coll Hosp NHS Fdn Trust, Inst Liver Studies, Denmark Hill, London SE5 9RS, England.;Kings Coll London, Fac Life Sci & Med, Inst Liver Studies, Sch Immunol & Microbial Sci, 125 Coldharbour Lane, London SE5 9NU, England.;Roger Williams Inst Hepatol, Fdn Liver Res, 111 Coldharbour Lane, London SE5 9NT, England.Science for Life Laboratory, SciLifeLab
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Hepatology: Elsevier BV76:2, s. 332-3420168-82781600-0641
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Till lärosätets databas
- Av författaren/redakt...
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Patel, Vishal C.
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Lee, Sunjae
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McPhail, Mark J. ...
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Da Silva, Kevin
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Guilly, Susie
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Zamalloa, Ane
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visa fler...
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Witherden, Eliza ...
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Stoy, Sidsel
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Vijay, Godhev Ku ...
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Pons, Nicolas
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Galleron, Nathal ...
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Huang, Xaiohong
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Gencer, Selin
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Coen, Muireann
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Tranah, Thomas H ...
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Wendon, Julia Al ...
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Bruce, Kenneth D ...
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Le Chatelier, Em ...
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Ehrlich, Stanisl ...
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Edwards, Lindsey ...
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Shoaie, Saeed
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Shawcross, Debbi ...
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visa färre...
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