Pathogenic Metagenomic Next-generation Sequencing to Optimize the Diagnosis of Decompensated Cirrhosis Infection
- Conditions
- Cirrhosis, Liver
- Registration Number
- NCT06039696
- Lead Sponsor
- Nanfang Hospital, Southern Medical University
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 850
- 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.
- Age > 80 years old.
- Malignancy of liver or other organs (including leukemia).
- Receiving immunosuppressive agents for non-hepatic diseases.
- HIV infection.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Positive rate of mNGS test in AD patients at enrolment
- Secondary Outcome Measures
Name Time Method 90-day transplantation-free mortality From enrollment to 90 days Incidence of acute kidney injury (AKI) From enrollment to 90 days 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.
Proportion of hospital readmissions due to infections From enrollment to 90 days Proportion of progression to SIRS or sepsis From enrollment to 90 days Consistency with blood culture results at enrollment Concordance of mNGS With Other traditional Testing on Pathogens
Incidence of CMV reactivation From enrollment to 90 days 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.
Rate of progression to acute-on-chronic liver failure (ACLF) From enrollment to 90 days 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).
Trial Locations
- Locations (1)
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China