Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure

Hartmann, Phillipp; Lang, Sonja; Schierwagen, Robert; Klein, Sabine; Praktiknjo, Michael; Trebicka, Jonel; Schnabl, Bernd

doi:10.1016/j.hbpd.2023.05.003

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…To identify fungal genera and species with the highest feature importance for detecting ALD vs NAFLD, we determined the mean decrease accuracy per random forest analysis, as described before. 32 , 33 Among the top genera differentiating ALD from NAFLD were Scopularopsis , Kluyveromyces , unidentified genera, Mucor , Saccharomyces , and Kazachstania ( Figure 2a ). Among the fungal species with the highest feature importance for detecting ALD vs NAFLD were S. cordiae , M. restricta , unknown species, S. cerevisiae , and C. albicans ( Figure 2b ).…”

Section: Resultsmentioning

confidence: 99%

“… 31 Area under the curve (AUC), best threshold to maximize the Youden index, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and p value between two AUCs of receiver operating characteristic (ROC) curves per DeLong method were calculated using the pROC library in R; and to identify fungal genera and species with the highest feature importance for detecting ALD cohorts vs NAFLD cohorts, the mean decrease accuracy was calculated with the randomForest library in R, as described. 32 , 33 Statistical analysis was performed using R statistical software, R version 1.3.1093 for Mac, 2020 the R Foundation for Statistical Computing.…”

Section: Methodsmentioning

confidence: 99%

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Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease

Viebahn,

Hartmann,

Lang

et al. 2024

Gut Microbes

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The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera Saccharomyces , Kluyveromyces , Scopulariopsis , and the species Candida albicans ( C. albicans ), Malassezia restricta ( M. restricta ), Scopulariopsis cordiae ( S. cordiae ) were significantly increased in patients with ALD, whereas the genera Kazachstania and Mucor were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of Scopulariopsis , Kluyveromyces , M. restricta , and Mucor to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised Scopulariopsis , Kluyveromyces , Mucor , M. restricta , and Kazachstania . For more advanced fibrosis stages (F2-F4), the fungal signature composed of Scopulariopsis , Kluyveromyces , Mucor , and M. restricta achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease

Viebahn,

Hartmann,

Lang

et al. 2024

Gut Microbes

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“…Bacteriophages targeting cytolytic E. faecalis as well as IgY antibody administration against cytolysin attenuate experimental ethanol-induced liver disease [46,47]. Fecal cytolysin did not predict disease severity in patients with liver cirrhosis and acute decompensation and in patients with acute on chronic liver failure, and the predictive value of cytolysin for mortality seems to be restricted to patients with alcohol-associated hepatitis [48]. Beneficial and butyrate producing fecal Faecalibacterium prausnitzii were decreased in patients with ALD as compared with healthy controls [49].…”

Section: Alcohol-associated Liver Diseasementioning

confidence: 92%

“…failure, and the predictive value of cytolysin for mortality seems to be restricted to patients with alcohol-associated hepatitis [48]. Beneficial and butyrate producing fecal Faecalibacterium prausnitzii were decreased in patients with ALD as compared with healthy controls [49].…”

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

The role of the microbiome in liver disease

Schöler,

Schnabl

2024

Current Opinion in Gastroenterology

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Purpose of review The intestinal microbiome and the gut-liver axis play a major role in health and disease. The human gut harbors trillions of microbes and a disruption of the gut homeostasis can contribute to liver disease. In this review, the progress in the field within the last 3 years is summarized, focusing on metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), autoimmune liver disease (AILD), and hepatocellular carcinoma (HCC). Recent findings Changes in the fecal virome and fungal mycobiome have been described in patients with various liver diseases. Several microbial derived metabolites including endogenous ethanol produced by bacteria, have been mechanistically linked to liver disease such as MASLD. Virulence factors encoded by gut bacteria contribute to ALD, AILD and HCC. Novel therapeutic approaches focused on the microbiome including phages, pre- and postbiotics have been successfully used in preclinical models. Fecal microbiota transplantation has been effective in attenuating liver disease. Probiotics are safe in patients with alcohol-associated hepatitis and improve liver disease and alcohol addiction. Summary The gut–liver axis plays a key role in the pathophysiology of liver diseases. Understanding the microbiota in liver disease can help to develop precise microbiota centered therapies.

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“…These findings suggest that cytolysin-positive E. faecalis may play a significant role in the development and progression of alcohol-associated hepatitis. However, the levels of cytolysin-positive E. faecalis do not serve as a predictive factor for disease severity in cases of acutely decompensated cirrhosis and acute-on-chronic liver failure nor in patients with non-alcoholic steatohepatitis [11,12], indicating that it could be a specific biomarker for alcohol-associated hepatitis.…”

Section: Introductionmentioning

confidence: 98%

Development of a Quantitative PCR Method for Detecting Enterococcus faecalis Cytolysin in Human Stool Samples

Cabré,

Yang,

Wang

et al. 2023

MPs

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Alcohol-associated liver disease (ALD) is a major global health issue, contributing significantly to morbidity and mortality worldwide. Among the ALD subtypes, alcohol-associated hepatitis poses a severe and urgent medical challenge with high short-term mortality rates. Despite extensive research, the current therapeutic approaches for alcohol-associated hepatitis have limited efficacy, necessitating novel interventions. Recent studies have highlighted the crucial role of the gut microbiota in ALD pathogenesis, particularly Enterococcus faecalis (E. faecalis) and its cytolysin exotoxin. This study presents the development of a standardized real-time quantitative polymerase chain reaction (RT-qPCR) assay to detect and quantify cytolysin in fecal samples from patients with alcohol-associated hepatitis. The diagnostic assay allows for an association analysis between cytolysin-positive E. faecalis and disease severity as well as mortality. This assay was developed to standardize the identification of cytolysin-positive patients who can be selected for clinical trials.

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Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure

Cited by 6 publications

References 26 publications

Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease

Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease

The role of the microbiome in liver disease

Development of a Quantitative PCR Method for Detecting Enterococcus faecalis Cytolysin in Human Stool Samples

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