Enhancing infection diagnostics in advanced chronic liver disease - harnessing clinical metagenomics for rapid pathogen and antimicrobial resistance detection

Sep 30, 2026

Uploaded by Kyle

Advanced chronic liver disease patients with cirrhosis are highly vulnerable to bacterial infections, which drive complications and mortality alongside escalating antimicrobial resistance. Traditional culture-based diagnostics are slow, labour-intensive, and frequently fail to provide timely, accurate results, delaying critical treatment decisions. Clinical metagenomics enables direct sequencing from patient-derived samples, supporting rapid pathogen identification and resistance profiling. Integrating point-of-care sequencing, standardized AMR databases, and bioinformatics workflows is key to improving diagnosis and outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

The burden of infection and antimicrobial resistance in advanced chronic liver disease

Limitations of current diagnostic standards

Clinical metagenomics for rapid pathogen and AMR detection

Implementation requirements and workflow needs

npj | antimicrobials & resistance Perspective [https://doi.org/10.1038/s44259-025-00171-7](https://doi.org/10.1038/s44259-025-00171-7) Enhancing infection diagnostics in advanced chronic liver disease: harnessing clinical metagenomics for rapid pathogen and antimicrobial resistance detection Check for updates | Merianne Mohamad1, Chrysi Sergaki2 & Vishal C. Patel1 | | | --- | --- | | Patients with advanced chronic liver disease who have underlying cirrhosis are highly susceptible to bacterial infections, which signiﬁcantly increase the risk of complications and mortality, compounded by escalating antimicrobial resistance. The current gold standard for infection detection and antimicrobial resistance (AMR) proﬁling remains dependant on traditional microbiological methods. These conventional approaches are slow, labour-intensive, and often fail to deliver timely and accurate results, delaying critical antimicrobial treatment decisions. Clinical metagenomics (CMg) is emerging asa transformative molecular-based tool in infection diagnostics. By enabling the direct sequencing of pathogens from patient-derived samples, CMg offers rapid and comprehensive identiﬁcation of pathogens and their resistance proﬁles. Incorporating this technology into the clinical management of patients with cirrhosis has potential to address diagnostic challenges, reduce reliance on broadspectrum antibiotics and improve outcomes. To effectively incorporate CMg into infection diagnostics, it will be essential to embed of point-of-care sequencing, standardisation of AMR databases, and accessibility to bioinformatics workﬂows. | | | The increasing burden of infections and antimicrobial resistance in advanced chronic liver disease and ongoing unmet needs of rapid infection diagnostics Cirrhosis represents an advanced stage of chronic liver disease (ACLD) and is marked by diminished liver synthetic function and clinical complications, resulting from sustained parenchymal injury and scarring. In the UK, it affects around 60,000 people, leading to recurrent hospitalisations and high mortality, contributing to over 4000 deaths annually1. Cirrhosis progresses from stable (‘compensated’) to decompensated stages, with the latter marked by complications that often require hospitalisation and can be lifethreatening, including portal hypertensive bleeding, ascites, spontaneous bacterial peritonitis and hepatic encephalopathy. Due to cirrhosisassociated immune dysfunction2 patients are particularly vulnerable to bacterial infections3, which can precipitate acute-on-chronic liver failure | (ACLF), characterised by multi-organ failure and extremely high short term mortality rates4.
A delay in the administration ofantibiotics in ACLDis associated with an increase of7.6%in mortality per hour in theﬁrst6 hofpresentation5. Ina nested cohort study of 635 patients with ACLD and septic shock who developed ACLF, in-hospital mortality was 75.6%6. The lack of rapid and accurate infection diagnostics has led to the frequent, poorly targeted and often inappropriate prescription of broad-spectrum antimicrobials, contributing to the increasing burden of antimicrobial resistance (AMR)7,8 further exacerbating infectious complications in patients with ACLD9.
The current gold standard for diagnosing bacterial infection in bioﬂuid samples (ascitic ﬂuid, blood, urine) obtained from patients with ACLD involves traditional culture-based microbiological methods, which are labour-intensive and often require long turnaround times. Samples undergo | 1Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Foundation for Liver Research and King’s College Hospital, London, UK. 2Science and Research, Medicines and Healthcare products Regulatory Agency, South Mimms, Hertfordshire, UK. [e-mail:](e-mail: vish.patel@kcl.ac.uk)[ vish.patel@kcl.ac.uk](e-mail: vish.patel@kcl.ac.uk) incubation

FAQs

Why are patients with advanced chronic liver disease at high risk of bacterial infections?

Cirrhosis-associated immune dysfunction makes these patients particularly vulnerable to bacterial infections, which can precipitate severe complications and drive mortality.

What are the key limitations of the current gold-standard infection diagnostics?

Traditional culture-based methods require prolonged incubation and additional laboratory steps, often producing delayed results and high rates of negative cultures, which can hinder timely antimicrobial decisions.

How does clinical metagenomics improve infection diagnostics in cirrhosis?

Clinical metagenomics enables direct sequencing of pathogens from patient-derived samples, providing rapid and comprehensive identification of pathogens and their antimicrobial resistance profiles.

Sep 30, 2026

Uploaded by Kyle