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Diagnostic Value and Clinical Application of mNGS for Post-Liver Transplantation Infection: A Cross-Sectional Study
Dong Zhao1, Liping Guo2, Dongli Lian2
1Division of Liver Surgery and Organ Transplantation Center, Shenzhen Third People's Hospital, Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.
Abstract:
Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p<0.0001) but lower specificity (35.71 vs. 89.28%; p<0.0001). Among the 48 kinds of pathogens detected, the Torque teno virus 22 (15/122) was the most common, followed by Primate erythroparvovirus 1 (13/122). The top four bacteria included Klebsiella pneumoniae (n = 8), Enterococcus faecium (n = 5), Stenotrophomonas maltophilia (n = 4), and Escherichia coli (n = 4). Aspergillus fumigatus was the most common fungus. The bronchoalveolar lavage fluid (BALF) exhibited the highest proportion of positive findings among sample types, with viral, fungal, and bacterial mixed infection being the most common (n = 6, 19.35%). Besides, using mNGS for early diagnosis of infection after liver transplantation may effectively prolong patient survival. This is the first study to explore the application value of mNGS and its comparison with traditional culture in pneumonia and other infections in post-liver transplantation patients. The simultaneous application of these two methods suggested that the Torque teno virus 22, Klebsiella pneumoniae, and the Aspergillus fumigatus are the most common pathogens of viruses, bacteria, and fungi after LT, suggesting that these pathogens may be associated with postoperative pathogen infection and patient prognosis. The mNGS technique showed distinct advantages in detecting mixed, viral, and parasitic infections in this patient population. Further studies are warranted to systematically elucidate the dynamic evolution and molecular characteristics of infection after liver transplantation.
Insights
Metagenomic next-generation sequencing (mNGS) offers higher sensitivity than traditional culture for diagnosing post-liver transplant infections. This advanced method aids in identifying common pathogens like Torque teno virus 22, Klebsiella pneumoniae, and Aspergillus fumigatus, potentially improving patient survival.
Area of Science:
- Infectious Diseases
- Transplant Surgery
- Molecular Diagnostics
Background:
- Liver transplantation is the definitive treatment for end-stage liver disease.
- Postoperative infections are a major cause of mortality following liver transplantation.
- Traditional diagnostic methods for infections have limitations in sensitivity and scope.
Purpose of the Study:
- To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for diagnosing infections in liver transplant recipients.
- To compare the performance of mNGS against traditional culture methods.
- To identify common pathogens responsible for infectious complications after liver transplantation.
Main Methods:
- Retrospective analysis of patients with infectious complications post-liver transplantation (July 2019 - December 2020).
- Inclusion of patients with pneumonia, unexplained fever, and other complications predisposing to infection.
- Application of mNGS for microbial detection, with results compared to conventional culture techniques.
Main Results:
- mNGS demonstrated significantly higher sensitivity (85.19%) compared to culture (22.22%) (p<0.0001), but lower specificity (35.71% vs. 89.28%) (p<0.0001).
- Torque teno virus 22 was the most frequently detected virus (15/122), followed by Primate erythroparvovirus 1 (13/122).
- Common bacterial pathogens included Klebsiella pneumoniae (n=8) and Enterococcus faecium (n=5); Aspergillus fumigatus was the most common fungus. Bronchoalveolar lavage fluid (BALF) showed the highest positive detection rate, with mixed infections being prevalent.
Conclusions:
- mNGS shows promise for early and comprehensive diagnosis of diverse infections, including viral and mixed types, after liver transplantation.
- The study identified Torque teno virus 22, Klebsiella pneumoniae, and Aspergillus fumigatus as key pathogens in post-liver transplant infections.
- Early diagnosis using mNGS may contribute to improved survival rates in liver transplant recipients experiencing infectious complications.

