Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial

Patel, Vishal C.; Lee, Sunjae; McPhail, Mark; Silva, Kévin Da; Guilly, Susie; Zamalloa, Ane; Witherden, Elizabeth A.; Støy, Sidsel; Vijay, Godhev K. Manakkat; Pons, Nicolas; Galleron, Nathalie; Huang, Xaiohong; Gencer, Selin; Coen, Muireann; Tranah, Thomas H.; Wendon, Julia; Bruce, Kenneth D.; Chatelier, Emmanuelle Le; Ehrlich, S. Dusko; Edwards, Lindsey; Shoaie, Saeed; Shawcross, Debbie L.

doi:10.1016/j.jhep.2021.09.010

Cited by 132 publications

(104 citation statements)

References 44 publications

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“…Changes in the gut microbiota profile are observed in any tract of the gastrointestinal system, including the oral mucosa [ 151 ]. Translocation to the gut of oral pathogens capable of degrading intestinal mucus has recently been demonstrated in cirrhotic patients with hepatic encephalopathy, suggesting that the oral-gut–liver axis is involved in the pathogenesis of liver disease complications [ 152 ].…”

Section: The Gut–liver Axismentioning

confidence: 99%

Intestinal Barrier in Human Health and Disease

Tommaso

Gasbarrini

Ponziani

2021

IJERPH

244

110

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The intestinal mucosa provides a selective permeable barrier for nutrient absorption and protection from external factors. It consists of epithelial cells, immune cells and their secretions. The gut microbiota participates in regulating the integrity and function of the intestinal barrier in a homeostatic balance. Pathogens, xenobiotics and food can disrupt the intestinal barrier, promoting systemic inflammation and tissue damage. Genetic and immune factors predispose individuals to gut barrier dysfunction, and changes in the composition and function of the gut microbiota are central to this process. The progressive identification of these changes has led to the development of the concept of ‘leaky gut syndrome’ and ‘gut dysbiosis’, which underlie the relationship between intestinal barrier impairment, metabolic diseases and autoimmunity. Understanding the mechanisms underlying this process is an intriguing subject of research for the diagnosis and treatment of various intestinal and extraintestinal diseases.

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Section: The Gut–liver Axismentioning

confidence: 99%

Intestinal Barrier in Human Health and Disease

Tommaso

Gasbarrini

Ponziani

2021

IJERPH

244

110

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“…Therefore, rifaximin-activated PXR may recover the intestinal barrier function by reducing intestinal permeability and gut endotoxin leakage in patients with cirrhosis. A recent clinical report also showed that rifaximin has a role in gut barrier repair by ameliorating bacterial translocation and systemic endotoxemia in patients with cirrhosis [ 45 ], which may improve the hepatic reserve.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study

Kawaratani

Kondo

Tatsumi

et al. 2022

JCM

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Background: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. Methods: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. Results: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin–bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child–Pugh C. Conclusions: The long-term rifaximin treatment was effective and safe for patients with HE, including Child–Pugh C.

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“…This evidence supports the hypothesis that rifaximin could exert other beneficial effects in addition to its antimicrobial effects, as previously described. 20,[22][23][24] In fact, alcohol exerts direct toxicity on the liver and promotes intestinal dysbiosis, which favours liver dysfunction. 25 Alcohol changes the composition and biodiversity of normal flora, which increases the levels of lipopolysaccharide and other toxic substances, leading to an increase in intestinal permeability.…”

Section: Adverse Effects Of Rifaximinmentioning

confidence: 99%

Effect of rifaximin on infections, acute‐on‐chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA‐AH)

Jimenez

Ventura-Cots

Sala

et al. 2022

Liver International

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Background & Aims Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. Methods This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end‐stage liver disease (MELD). We evaluated bacterial infections, liver‐related complications, mortality and liver function tests after 90 days. Results Twenty‐one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute‐on‐chronic liver failure (ACLF) linked to infections within the treatment group. Liver‐related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. Conclusions Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.

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Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial

Cited by 132 publications

References 44 publications

Intestinal Barrier in Human Health and Disease

Intestinal Barrier in Human Health and Disease

Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study

Effect of rifaximin on infections, acute‐on‐chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA‐AH)

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