Anti-infection Therapy Based on mNGS Etiological Diagnosis and Infection After Liver Transplantation

The Effect of Donor-oriented Anti-infection Therapy Based on mNGS Etiological Diagnosis on the Incidence of Perioperative Infection and Prognosis of Corresponding Recipients After Liver Transplantation

Liver transplantation is the most efficacious treatment for end-stage liver disease; however, postoperative infection remains a major complication and leading cause of recipient mortality. Specifically, infections originating from donors, particularly those caused by multidrug-resistant bacteria, can significantly impact the prognosis of liver transplant recipients. Theoretically, implementing targeted antimicrobial therapy for donors prior to organ donation could reduce the likelihood of pathogen transmission with the transplanted organ, thereby potentially decreasing the incidence of post-transplant infections from donor sources and improving recipient outcomes. Nevertheless, there is currently a dearth of high-quality prospective studies in this domain. Our previous investigation (Front Microbiol. 2022 Jul 1;13:919363) demonstrated that second-generation metagenomic sequencing (mNGS) technology holds substantial value in expeditious pathogen screening following liver transplantation. Prompt implementation of targeted treatment based on microbiological findings has shown potential to enhance outcomes for select recipients. Therefore, this study aims to provide tailored treatment for donors based on microbiological examination results (including mNGS detection and culture results), analyze corresponding data regarding recipient infection occurrence and prognosis, and explore the impact of mNGS-guided donor antimicrobial therapy on perioperative infection rates among liver transplant recipients.

Study Overview

• Status: Not yet recruiting
• Conditions: Infection
• Intervention / Treatment: Diagnostic test: mNGS

Detailed Description

Liver transplantation has been established as a highly effective treatment for end-stage liver disease, with continuous advancements in surgical techniques and immunosuppressive regimens significantly improving success rates and long-term survival for recipients. Despite these strides, postoperative challenges persist, with infections remaining a major complication and a leading cause of recipient mortality. Pathogens typically arise from the recipient's lungs, intestines, or other sites, yet donor-derived infections (DDIs), particularly those involving multidrug-resistant organisms, pose a substantial threat to transplant recipients' prognosis, prompting increased attention from liver transplant surgeons. Conventional microbial culture, with its lower positivity rate compared to metagenomic next-generation sequencing (mNGS), exhibits a limited ability to guide clinically targeted anti-infective treatment. Hence, the rapid and accurate identification of pathogens, coupled with early targeted anti-infective treatment, is pivotal for effective post-transplant infection management and DDI prevention. Theoretically, preemptive identification of microbiological diagnoses before organ donation, followed by targeted anti-infective treatment for the donor, holds the potential to diminish the risk of pathogens entering the recipient's body with the donated organ. This reduction may subsequently decrease the risk of post-transplant recipient infection originating from the donor, ultimately enhancing the recipient's prognosis. However, as of now, there is a dearth of relevant clinical research on this topic. Notably, our transplantation center employs mNGS to screen both donor and recipient pathogens, a method progressively gaining widespread clinical application. Through a comprehensive analysis of results from both detection methods, we implement targeted anti-infective treatment for both donors and recipients. Consequently, by analyzing cases of liver transplantation and their corresponding donor cases at our center, this study aims to investigate the impact of donor anti-infective treatment guided by mNGS microbiological diagnosis on the incidence of perioperative infections in recipients undergoing liver transplantation. The analysis encompasses the occurrence of infections, results of microbiological examinations, and the formulation of corresponding anti-infective treatment plans.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Dong Zhao, Dr.; Phone Number: 13631508530; Email: zdong1233@126.com

Study Locations

• China
  • Shenzhen
    • Shenzhen, Shenzhen, China
      • Shenzhen Third People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients treated with Liver transplantation

Description

Inclusion Criteria:

• Recipient age >18 years;
• Clinical diagnosis of infection in the donor with administered anti-infective treatment;
• Complete clinical data for both the donor and recipient.

Exclusion Criteria:

• Recipient age <18 years;
• Presence of surgery-related factors leading to death or infection, such as intraoperative cardiac arrest resulting in postoperative death, intraoperative bleeding exceeding 2000ml, postoperative complications like intestinal or bile leakage, graft dysfunction, or small liver syndrome;
• Incomplete clinical data for the donor or recipient

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
donor-mNGS-testing group; Organ donors are treated with mNGS testing before organ donation	Diagnostic test: mNGS; metagenomics next generation sequencing
donor-non-mNGS-testing group; Organ donors are not treated with mNGS testing before organ donation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection	The diagnosis of infection relies on a comprehensive assessment of clinical manifestations, microbiological test results, imaging examinations, and related laboratory tests. In our study, this diagnosis was established by a team of infectious disease specialists and organ transplant physicians. Donor-derived infection occurs when pathogens present in the donor's body post-organ procurement lead to the recipient contracting an infection with the same pathogens during the organ transplantation process.	The study focused on the incidence of infection and the postoperative prognosis of transplant recipients within 30 days

Collaborators and Investigators

• Sponsor: Shenzhen Third People's Hospital
• Investigators: Principal Investigator: Dong Zhao, Dr., Shenzhen Third People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: SZSPH-LT-mNGS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No