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mNGS improves the efficiency of infection diagnosis and treatment in acute-on-chronic liver failure
Yushan Liu1,2,3,4, Qiao Zhang1,2,3,4, Juan Li1,2,3,4
1Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Road(W), Xi'an City, Shaanxi Province, China.
Introduction:
The early diagnosis of infections in acute-on-chronic liver failure (ACLF) is still difficult. mNGS(metagenomic next-generation sequencing) is a no-bias, sensitive pathogen diagnosis method, and further research on mNGS in ACLF is needed.
Methods:
A total of 275 ACLF patients with suspected or confirmed infections were recruited and divided into the mNGS group and the non-mNGS group. Differences between the two groups were assessed.
Results:
The 1:1 Propensity score matching (PSM) for balancing the baseline variables produced 86 patients in each group. From these 86 patients in the mNGS group, 134 samples were collected and analyzed. The overall microbiological positive rate (103/134, 76.9%) detected by mNGS was higher than that detected by culture (24/134, 17.9%), particularly for fungi (14.9% vs. 2.2%). The etiological diagnosis rates for pulmonary and thoracoabdominal infections detected by the mNGS method were higher than those of the culture method (47.9% vs. 11.4%; 52.0% vs. 18.4%, respectively). The etiological diagnosis can be confirmed 22.83 ± 26.27 h ahead of time. mNGS testing did not significantly improve 90-day transplant-free survival in the overall cohort (sHR 0.96, 95% CI 0.72-1.27; P = 0.76). In the subgroup where mNGS guided therapy, numerically higher resolution rates were observed for pulmonary (53.8% vs 37.1%), abdominal (63.2% vs 52.6%), and bloodstream infections (66.7% vs 50.0%), though these differences were not statistically significant.
Conclusions:
mNGS is a valuable diagnostic tool for ACLF with infections, especially for viruses and fungi. mNGS allows for precise and earlier pathogen diagnosis, enabling timely and targeted anti-infective therapy. mNGS may be associated with improved clinical outcomes in ACLF patients with co-infections, though this potential association requires further validation.
Trial Registration:
The study was registered on Clinicaltrials.gov (registration number: NCT05740696, release date: February22,2023). Accessible at: https://classic.
Clinicaltrials:
gov/ct2/show/NCT05740696.
Insights
Metagenomic next-generation sequencing (mNGS) offers a more sensitive method for diagnosing infections in acute-on-chronic liver failure (ACLF) patients. While it enables earlier pathogen identification, its impact on transplant-free survival requires further investigation.
Area of Science:
- Infectious Diseases
- Hepatology
- Genomics
Background:
- Diagnosing infections in acute-on-chronic liver failure (ACLF) is challenging.
- Metagenomic next-generation sequencing (mNGS) is a sensitive, unbiased method for pathogen detection.
- Further research on mNGS utility in ACLF is warranted.
Purpose of the Study:
- To evaluate the diagnostic performance of mNGS compared to conventional methods in ACLF patients with suspected infections.
- To assess the impact of mNGS on clinical outcomes and treatment timing.
Main Methods:
- A cohort of 275 ACLF patients with suspected infections was divided into mNGS and non-mNGS groups.
- Propensity score matching (PSM) was used to create comparable groups of 86 patients each.
- Pathogen detection rates and time to diagnosis were compared between mNGS and culture-based methods.
Main Results:
- mNGS demonstrated a higher overall microbiological positive rate (76.9%) compared to culture (17.9%), especially for fungi.
- Etiological diagnosis rates were significantly higher with mNGS for pulmonary (47.9% vs. 11.4%) and thoracoabdominal infections (52.0% vs. 18.4%).
- mNGS enabled diagnosis approximately 22.8 hours earlier, but did not significantly improve 90-day transplant-free survival in the overall cohort.
Conclusions:
- mNGS is a valuable tool for early and precise pathogen diagnosis in ACLF infections, particularly for viruses and fungi.
- It facilitates timely, targeted anti-infective therapy.
- mNGS may improve clinical outcomes in ACLF co-infections, but requires further validation.
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