Fecal gelatinase does not predict mortality in patients with alcohol-associated hepatitis
Authors:Yongqiang Yang1,a, Philipp Hartmann2,3,a and Bernd Schnabl1,4
doi: 10.15698/mic2024.08.836
Volume 11, pp. 328 to 338, published 26/08/2024.
1 Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. 2 Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA. 3 Division of Gastroenterology, Hepatology & Nutrition, Rady Children’s Hospital San Diego, CA, 92123, San Diego, USA. 4 Department of Medicine, VA San Diego Healthcare System, CA, 92161, San Diego, USA.
Keywords:
alcoholic hepatitis, Enterococcus faecalis, microbiota, microbiome.
Corresponding Author(s):
Conflict of interest statement:
B.S. has been consulting for Ambys Medicines, Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, Surrozen and Takeda. B.S. is founder of Nterica Bio. UC San Diego has filed several patents with B.S. as inventor related to this work. B.S.’s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, ChromoLogic, CymaBay Therapeutics, Intercept Pharmaceuticals, NGM Biopharmaceuticals, Prodigy Biotech and Synlogic Operating Company. P.H.’s institution UC San Diego has received research support from Nterica Bio.
Please cite this article as:
Yongqiang Yang, Phillipp Hartmann, Bernd Schnabl (2024). Fecal gelatinase does not predict mortality in patients with alcohol-associated hepatitis. Microbial Cell 11: 328-338. doi: 10.15698/mic2024.08.836
© 2024 Yang et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Alcohol-associated liver disease is highly prevalent worldwide, with alcohol-associated hepatitis as a severe form characterized by substantial morbidity, mortality, and economic burden. Gut bacterial dysbiosis has been linked to progression of alcohol-associated hepatitis. Fecal cytolysin secreted by the pathobiont Enterococcus faecalis (E. faecalis) is associated with increased mortality in patients with alcohol-associated hepatitis. Although gelatinase is considered a virulence factor in E. faecalis, its prevalence and impact on alcohol- associated hepatitis patient outcomes remains unclear. In this study, 20 out of 65 (30.8%) patients with alcohol-associated hepatitis tested positive for gelatinase in their stool. There were no significant differences in 30-day and 90-day mortality between gelatinase-positive and gelatinase-negative patients (p=0.97 and p=0.48, respectively). Fecal gelatinase had a low discriminative ability for 30-day mortality (area under the curve [AUC] 0.50 vs fibrosis-4 Index (FIB-4) 0.75) and 90-day mortality compared with other established liver disease markers (AUC 0.57 vs FIB- 4 0.79 or ‘age, serum bilirubin, INR, and serum creatinine’ (ABIC) score 0.78). Furthermore, fecal gelatinase was not an important feature for 30-day or 90-day mortality per random forest analysis. Finally, gelatinase-positive patients with alcohol-associated hepatitis did not exhibit more severe liver disease compared with gelatinase-negative patients. In conclusion, fecal gelatinase does not predict mortality or disease severity in patients with alcohol-associated hepatitis from our cohort.