Highlights
- •A non-hepatotropic viral signature was identified in individuals with AD of cirrhosis.
- •This viral signature correlated with clinical outcomes.
- •CMV reactivation might play a pathogenic role in AD and progression toward ACLF.
- •Further refinement and validation are needed to define the clinical relevance of our results.
Background & Aims
Although the effect of bacterial infection on cirrhosis has been well-described, the
effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated
the genome fragments of circulating microorganisms using metagenomic next-generation
sequencing (mNGS) in individuals with acute decompensation (AD) of cirrhosis, focusing
on NHVs, and related the findings to clinical outcomes.
Methods
Plasma mNGS was performed in 129 individuals with AD of cirrhosis in the study cohort.
Ten healthy volunteers and 20, 39, and 81 individuals with stable cirrhosis, severe
sepsis and hematological malignancies, respectively, were enrolled as controls. Validation
assays for human cytomegalovirus (CMV) reactivation were performed in a validation
cohort (n = 58) and exploratory treatment was instituted.
Results
In the study cohort, 188 microorganisms were detected in 74.4% (96/129) of patients,
including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). A
NHV signature was identified in individuals with AD, and CMV was the most frequent
NHV, which correlated with the clinical effect of empirical antibiotic treatment,
progression to acute-on-chronic liver failure, and 90-day mortality. The NHV signature
in individuals with acute-on-chronic liver failure was similar to that in those with
sepsis and hematological malignancies. CMV was detected in 24.1% (14/58) of patients
in the validation cohort. Of the 14 cases with detectable CMV by mNGS, nine were further
validated by real-time PCR or pp65 antigenemia testing. Three patients with CMV reactivation
received ganciclovir therapy in an exploratory manner and experienced clinical resolutions.
Conclusions
The results of this study suggest that NHVs may play a pathogenic role in complicating
the course of AD. Further validation is needed to define whether this should be incorporated
into the routine management of individuals with AD of cirrhosis.
Impact and implications
A non-hepatotropic virus (NHV) signature, which was similar to that in individuals
with sepsis and hematological malignancies, was identified in individuals with acute
decompensation of cirrhosis. The detected viral signature had clinical correlates,
including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic
liver failure and short-term mortality. Cytomegalovirus reactivation, which is treatable,
may adversely affect clinical outcomes in some individuals with decompensated cirrhosis.
Routine screening for NHVs, especially cytomegalovirus, may be useful for the management
of individuals with acute decompensation of cirrhosis.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: October 26, 2022
Accepted:
October 11,
2022
Received in revised form:
September 13,
2022
Received:
April 9,
2022
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