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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
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L actococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis
Lore Van Espen1, Maximilian Joseph Brol2, Lila Close1
1KU Leuven, Department of Microbiology, Immunology, & Transplantation, Rega Institute, Division of Clinical & Epidemiological Virology, Laboratory of Viral Metagenomics, Belgium.
JHEP Reports : Innovation in Hepatology
|December 24, 2025
Summary
The gut virome changes in cirrhosis, with specific phages predicting acute-on-chronic liver failure (ACLF) and bacterial infections. These phage alterations are linked to increased mortality risk in patients with advanced liver disease.
Area of Science:
- Gastroenterology and Hepatology
- Microbiology
- Virology
Background:
- Portal hypertension in cirrhosis compromises gut barrier integrity, leading to bacterial translocation, endotoxemia, and systemic inflammation.
- Gut phages significantly influence bacteria-host interactions, playing a crucial role in the progression of liver disease complications.
- The human gut virome's role in decompensated cirrhosis and acute-on-chronic liver failure (ACLF) remains under-investigated.
Purpose of the Study:
- To investigate the role of the human gut virome in the context of acute decompensation of cirrhosis and ACLF.
- To identify specific phage groups associated with ACLF development and bacterial infections.
- To assess the prognostic value of gut phage alterations in patients with decompensated cirrhosis.
Main Methods:
- Longitudinal assessment of fecal virome using metagenomic sequencing in two independent patient cohorts (n=187).
- Analysis included descriptive characterization, phage host prediction, lifestyle classification, and association with clinical parameters.
- Patients included those with acute decompensation or ACLF, and those with decompensated cirrhosis undergoing TIPS surgery.
Main Results:
- Phage alpha-diversity was elevated in ACLF patients and correlated with disease severity.
- A shift from virulent to temperate phages was observed in ACLF.
- Lactococcus A phages predicted ACLF development (OR=14), while Enterococcus B phages and their hosts were linked to bacterial infection (OR=14.7).
- Both phage families were associated with increased 90-day mortality.
Conclusions:
- ACLF is characterized by increased gut virome diversity and a shift towards temperate phages.
- Lactococcus A phages are linked to ACLF development, and Enterococcus B phages to bacterial infection.
- Gut virome analysis holds potential for patient stratification in clinical practice for liver disease management.
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