Dataset Information

The impact of rifaximin on inflammation and metabolism in alcoholic hepatitis: A randomized clinical trial.

ABSTRACT:

Background and aims

Alcoholic hepatitis (AH) is characterized by acute liver failure, neurocognitive impairment and renal failure. Severe inflammatory reactions are also known to occur in AH. Inflammation and bacterial translocation in the gut are thought to have major impact on disease development and progression. The mortality rate for AH is close to 50%. We aimed to assess the efficacy of rifaximin in treating AH and its impact on inflammation and metabolism.

Methods

The trial was approved by relevant authorities (EudraCT no: 2014-02264-33, Scientific Ethics Committee, jr. no: H-1-2014-056). Primary outcomes were changes in metabolic and inflammatory markers. Secondary outcomes were portal hypertension, kidney and neurocognitive function.

Results

Thirty-two patients were randomized to standard medical therapy (SMT) or SMT plus rifaximin, allocation was concealed. Four patients in the SMT group and five patients in the SMT + rifaximin group died due to AH and liver failure. No adverse events related to the study medication were observed. We found no significant differences in amino acids or inflammation markers (IL-2, IL-6, IL-8, IL-10, TNF-α, interferon-γ) between the groups after 28 and 90 days.

Conclusion

Rifaximin does not alter inflammation or metabolism in patients with AH.

SUBMITTER: Kimer N

PROVIDER: S-EPMC8920190 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

The impact of rifaximin on inflammation and metabolism in alcoholic hepatitis: A randomized clinical trial.

Kimer Nina N Meldgaard Mads M Hamberg Ole O Kronborg Thit Mynster TM Lund Allan M AM Møller Holger Jon HJ Bendtsen Flemming F Ytting Henriette H

PloS one 20220314 3

<h4>Background and aims</h4>Alcoholic hepatitis (AH) is characterized by acute liver failure, neurocognitive impairment and renal failure. Severe inflammatory reactions are also known to occur in AH. Inflammation and bacterial translocation in the gut are thought to have major impact on disease development and progression. The mortality rate for AH is close to 50%. We aimed to assess the efficacy of rifaximin in treating AH and its impact on inflammation and metabolism.<h4>Methods</h4>The trial ...[more]

PMID: 35286322

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Project description:BACKGROUND: Alcohol-related liver disease ranges from silent alcoholic steatohepatitis (sASH), an asymptomatic and compensated phenotype, to life- threatening alcoholic hepatitis (AH). A systematic comparative study of the clinical, histological and molecular features of these subtypes is lacking. METHODS : Two large cohorts of patients were recruited in an international, observational multi-center study: a retrospective cohort of patients with sASH (n=110) and a prospective cohort of patients with AH (two subgroups with n=121 and 104). sASH and AH were compared by doing clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis. FINDINGS: Age and mean alcohol intake were similar in patients with sASH vs AH. AH showed lower mean arterial pressure than sASH. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma- glutamyl transferase levels than AH. Individuals with AH demonstrated profound liver failure, lower blood pressure and increased mortality. Histologically, the grade of steatosis, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and progenitor cell expansion were more frequent among AH patients. One-year mortality was 10% in sASH and 50% in AH. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. Globally, AH patients exhibited changes in 4,921 genes, while the number of dysregulated genes in sASH patients was less pronounced -1,327-. While sASH was characterized by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. INTERPRETATION: Despite comparable daily alcohol intake, AH patients presented with worse liver function and hemodynamic status compared to sASH. Bilirubinostasis, severe fibrosis and progenitor cell expansion were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared to sASH.

Project description:BackgroundRecent evidence suggests the systemic accumulation of by-products of gut microbes contributes to cardiovascular morbidity in patients with CKD. Limiting the generation of toxic bacterial by-products by manipulating the intestinal microbiota may be a novel strategy for reducing cardiovascular disease in CKD. Rifaximin is a minimally absorbed, oral antibiotic that targets intestinal pathogens and is commonly used as chronic therapy for the prevention of encephalopathy in patients with cirrhosis.MethodsWe conducted a randomized, double-blinded, placebo-controlled trial to determine the effect of a 10-day course of oral rifaximin 550 mg BID versus placebo on circulating concentrations of gut-derived cardiovascular toxins and proinflammatory cytokines in patients with stage 3-5 CKD (n=38). The primary clinical outcome was change in serum trimethylamine N-oxide (TMAO) concentrations from baseline to study end. Secondary outcomes included change in serum concentrations of p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines (C-reactive protein, IL-6, IL-1β), and change in composition and diversity of fecal microbiota.ResultsA total of 19 patients were randomized to each of the rifaximin and placebo arms, with n=17 and n=14 completing both study visits in these respective groups. We observed no difference in serum TMAO change (post-therapy minus baseline TMAO) between the rifaximin and placebo groups (mean TMAO change -3.9±15.4 for rifaximin versus 0.5±9.5 for placebo, P=0.49). Similarly, we found no significant change in serum concentrations for p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines. We did observe differences in colonic bacterial communities, with the rifaximin group exhibiting significant decreases in bacterial richness (Chao1, P=0.02) and diversity (Shannon H, P=0.05), along with altered abundance of several bacterial genera.ConclusionsShort-term rifaximin treatment failed to reduce gut-derived cardiovascular toxins and inflammatory cytokines in patients with CKD.Clinical trial registry name and registration numberRifaximin Therapy in Chronic Kidney Disease, NCT02342639.

Dataset Information

The impact of rifaximin on inflammation and metabolism in alcoholic hepatitis: A randomized clinical trial.

Background and aims

Methods

Results

Conclusion

Publications

The impact of rifaximin on inflammation and metabolism in alcoholic hepatitis: A randomized clinical trial.

Similar Datasets

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