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Rifaximin-alpha reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy : RIFSYS randomised controlled trial
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- Patel, Vishal C. (författare)
- 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.
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- Lee, Sunjae (författare)
- KTH,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.
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- McPhail, Mark J. W. (författare)
- 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.
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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)
- Elsevier BV, 2022
- 2022
- Engelska.
- Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:2, s. 332-342
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- Hepatic encephalopathy
- rifaximin-alpha
- cirrhosis
- systemic inflammation
- gut microbiome
- salivary microbiome
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