Abstract

BackgroundDespite the obvious advantages of metagenomic next-generation sequencing (mNGS) in etiological diagnosis of various infectious diseases, there are few reports on etiological diagnosis of suspected thoracic and abdominal infections in patients with end-stage liver disease (ESLD).MethodsSeventy-three ESLD patients were enrolled from January 2019 to May 2021 due to suspected complicated thoracic and abdominal infections with poor response to empirical anti-infective treatment. Pleural effusion and ascites samples of these patients were collected for mNGS detection and conventional pathogen culture. The application value of mNGS in etiological diagnosis of thoracic and abdominal infections in ESLD patients was finally evaluated.ResultsA total of 96 pathogens were detected using mNGS method, including 47 bacteria, 32 viruses, 14 fungi, 2 Mycobacterium tuberculosis, and 1 parasite. The positive rate of mNGS reached 42.5%, which was significantly higher than that of conventional culture method (21.9%) (p = 0.008). Considering neutrophil counts, the overall positive rate of bacteria detection of both methods in Polymorphonuclear Neutrophils (PMN) ≥250/mm3 group was 64.3% and in PMN <250/mm3 group was 23.7%. Compared with the final clinical diagnosis, the agreement rate of mNGS in patients with positive bacteria detection and with suspected positive bacteria detection was 78.6% (11/14) and 44.4% (8/18), respectively. In addition, the agreement rate of mNGS was 66.7% (4/6, respectively) in patients with positive and suspected fungal detection. Interestingly, of the 11 patients with fungal detection, 5 had alcoholic liver disease, accounting for 45.5% of all patients with alcoholic liver disease. We also detected 32 strains of viruses using mNGS, mainly cytomegalovirus (62.5%).ConclusionsThe mNGS method is a useful supplement to conventional culture methods, which performs a higher positive rate, higher sensitivity, and broader pathogen spectrum, especially for rare pathogens and those difficult to culture. For ESLD patients, mNGS has great prospects in early etiological diagnosis of thoracic and abdominal infections. In addition, the cutoff values for the diagnosis of bacterial infection (PMN ≥250/mm3) in the thoracic and abdominal cavities may need to be redefined.

Highlights

  • End-stage liver disease (ESLD) refers to the late stage of liver disease caused by various liver injuries, mainly the decompensated stage of liver cirrhosis and liver failure due to various reasons (Kamath et al, 2007; Trebicka et al, 2021)

  • The 73 enrolled ESLD patients consisted of 49 males (67.1%) and 24 females (32.9%)

  • Distribution of Pathogens Detected by Metagenomic Next-Generation Sequencing and Culture

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Summary

Introduction

End-stage liver disease (ESLD) refers to the late stage of liver disease caused by various liver injuries, mainly the decompensated stage of liver cirrhosis and liver failure due to various reasons (Kamath et al, 2007; Trebicka et al, 2021). Due to the impact of multiple factors such as portal hypertension, hypoproteinemia, and bacterial translocation, secondary thoracic and abdominal infection is the most common type of infection in ESLD patients, complicated with a large amount of pleural effusion and ascites (Gentilini et al, 2002; European Association for the Study of the L, 2010; Pericleous et al, 2016; Song, 2018). For patients with poor responses to empirical anti-infective treatment and still suspected of having thoracic and abdominal infections, the mortality risk will further increase in the absence of targeted treatment. Despite the obvious advantages of metagenomic next-generation sequencing (mNGS) in etiological diagnosis of various infectious diseases, there are few reports on etiological diagnosis of suspected thoracic and abdominal infections in patients with end-stage liver disease (ESLD)

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