Plasma microbial cell-free DNA metagenomic sequencing for early detection of infection after liver transplantation: a prospective cohort study

Abstract

Microbial cell-free DNA (mcfDNA) metagenomic next-generation sequencing (mNGS) is a promising technique for diagnosing infectious diseases. However, research on mcfDNA-based mNGS for diagnosing infections in liver transplantation (LT) recipients remains limited. The aim of this study was to evaluate the diagnostic performance and clinical utility of plasma mcfDNA mNGS during the early post-LT period. In this prospective diagnostic cohort study, adult LT recipients underwent plasma mcfDNA mNGS on postoperative days 7 and 14. The findings were compared with results of the blood cultures and other conventional microbiological tests at the species level. Among 193 LT recipients, mNGS positivity was observed in 14.5% on day 7 and 21.8% on day 14. The concordance between mNGS and blood culture for bacterial pathogens was modest on days 7 (35.0%) and 14 (14.3%) but increased substantially when other clinically relevant specimens were included (80.0% and 71.4%, respectively). mNGS identified additional pathogens not detected using blood culture in 59.3% and 74.2% of cases on days 7 and 14, respectively. Viral pathogens, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and roseolovirus, were also detected. Among the 13 discordant cases (blood culture-positive and mNGS-negative), two (15.4%) were classified as contamination/colonization, five (38.5%) as weak positives, and six (46.2%) as not detected by mNGS. Plasma mcfDNA mNGS demonstrated substantial concordance with conventional microbiological testing when clinically relevant specimens were considered. mNGS may serve as a useful adjunct tool for early pathogen detection and clinical assessment of LT recipients.