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Updated: Jan 8, 2026

Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
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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
PubMed
Abstract

Insights

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.
Keywords:
acute-on-chronic liver failureacutely decompensated cirrhosisfecal microbiomefecal viromegut phagesphage host prediction

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