Pathogenic Metagenomic Next-generation Sequencing to Optimize the Diagnosis of Decompensated Cirrhosis Infection

Clinical Application of Pathogenic Metagenomic Next-generation Sequencing to Optimize the Diagnosis of Decompensated Cirrhosis Infection: a Multicenter, Prospective Study

The goal of this observational study is to learn about clinical application of pathogenic metagenomic next-generation sequencing to optimize the diagnosis of infection in decompensated cirrhotic patients. The main questions it aims to answer are:

1. mNGS testing in optimizing anti-infective drug use in patients with acute decompensation, including response to empiric antibiotic therapy.
2. Proportion of patients with re-compensation.
3. The positive rate of mNGS in patients with acute decompensated cirrhosis and the characteristics of pathogen.
4. The incidence, risk factors and clinical correlation of CMV reactivation.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis, Liver

Detailed Description

Metagenomic next-generation sequencing (mNGS) is emerging as an important culture-independent technique that can detect nearly all known pathogens simultaneously from a clinical sample.Sequencing of microbial cell-free DNA (cfDNA) has recently been shown to enable diagnosis of several infection. Relevant studies on the clinical application of mNGS in cirrhosis patients are rare. The primary aim of this study was to comprehensively evaluate the fragments of genomic DNA from circulating microorganisms in acutely decompensated cirrhosis patients by sequencing the microbial cfDNA and relate this to clinical outcomes. The secondary aim was to validate the potential role of CMV reactivation, a known NHV with available antiviral medicines, in determining the prognosis of decompensated cirrhosis patients.

• Study Type: Observational
• Enrollment (Estimated): 850

Contacts and Locations

• Study Contact: Name: CHEN Jinjun; Phone Number: +86 020 62787310; Email: chjj@smu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Nanfang Hospital
      • Contact: CHEN Jinjun; Phone Number: +86 020 62787310; Email: chjj@smu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patient with diagnosis of cirrhosis hospitalized for acute decompensation

Description

Inclusion Criteria:

• Age ≥ 18 years old.
• Diagnosis of cirrhosis, previously known or not, of any etiology, histologically proven or not.
• Acute decompensation: ascites, digestive hemorrhage or hepatic encephalopathy.

Exclusion Criteria:

• Age > 80 years old.
• Malignancy of liver or other organs (including leukemia).
• Receiving immunosuppressive agents for non-hepatic diseases.
• HIV infection.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
patients received mNGS test; After enrolment, patients will receive mNGS test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Positive rate of mNGS test in AD patients	at enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistency with blood culture results	Concordance of mNGS With Other traditional Testing on Pathogens	at enrollment
Incidence of CMV reactivation	Cytomegalovirus DNA was quantified in stored plasma samples using real-time PCR (polymerase chain reaction) assay. DNA extraction was performed on 200 µL of plasma using a QIAamp DNA blood kit (Qiagen, German). Then, 25 µL of Tris (10 mM, pH 8.0) was used to elute the DNA, and 10 µL of the DNA was used for each PCR reaction. The minimum detection level was 102 copies/ml of plasma and values over this lower detection limit were considered to be CMV reactivation positive.	From enrollment to 90 days
90-day transplantation-free mortality		From enrollment to 90 days
Incidence of acute kidney injury (AKI)	AKI is defined as a change in SCr of ≥ 0.3 mg/dl (26.5 μmol/L) in ≤ 48 h, or a 50% increase in SCr from a baseline that is known or presumed to have occurred in the past 7 days.	From enrollment to 90 days
Proportion of hospital readmissions due to infections		From enrollment to 90 days
Proportion of progression to SIRS or sepsis		From enrollment to 90 days
Rate of progression to acute-on-chronic liver failure (ACLF)	ACLF was defined according to the European Association for the Study of Liver-Chronic Liver Failure (EASL-CLIF) criteria. ACLF grade-1 includes three subgroups: 1) patients with single kidney failure; 2) patients with single failure of the liver, coagulation, circulation or respiration, who had serum creatinine ranging from 1.5 to 1.9 mg/dl and/or mild-to-moderate hepatic encephalopathy; and 3) patients with single cerebral failure who had serum creatinine ranging from 1.5 and 1.9 mg/dl. ACLF grade-2: patients with two organs failure. ACLF grade-3: patients with three organ failures or more. ACLF development: patients with absence of ACLF on admission and progression to ACLF within 28 days. The severity of liver disease was evaluated by the model of end-stage liver disease (MELD) score, Child-Pugh score and CLIF-AD score (in those without ACLF).	From enrollment to 90 days

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Principal Investigator: Chen Jinjun, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: September 10, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: NFEC-2020-255

Drug and device information, study documents

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