Analysis of proteins to differentiate between infected and non-infected ACLF patients

Completed

Conditions: Fibrosis and cirrhosis of liver,

Registration Number: CTRI/2021/12/038725

Lead Sponsor: Post Graduate Institute of Medical Education and Research PGIMER

Brief Summary: Acute on Chronic Liver Failure (ACLF) is acatastrophic event in patients with cirrhosis that carries high mortality.Immune paresis observed in ACLF predisposes to multiple infections and sepsisremains the most common reason for admission, multi-organ failures andmortality in such patients. Often, there is a significant overlap in systemicinflammatory response due to ACLF per se (sterile inflammation) and due toinfections (sepsis) that lead to misuse of broad-spectrum antimicrobials; evenin the absence of true sepsis. Moreover, there is a great dilemma indifferentiating fungal sepsis from bacterial sepsis. Also, the understanding asto why certain patients develop bacterial and others develop fungal infectionsremains uncertain. Current diagnostics for sepsis relies on cultures (yield:50% in bacterial and 20-30% in fungal infections) and biomarkers that lacksensitivity, negative predictive value and are often delayed in patients withACLF. Early diagnosis and adequate treatment of sepsis remain an unmet goal inthese patients

A novel technique of untargeted proteomics with a highthroughput strategy of liquid chromatography and mass spectrometry (LC/MS) canidentify whole proteome and the final effectors in any biological system. Itmay help identify unique protein signatures as well as pathways associated witha disease or condition. In this project, we aim to elucidate differences inplasma proteomics and clinical profile in ACLF patients with and without sepsis(bacterial/fungal) and find associations with the final outcomes. In addition,we will ascertain the pathophysiology of sepsis in ACLF using this approach.

The study will be conducted in two phases: discovery andverification. In the discovery phase, the consecutive non-repetitive patientswith ACLF admitted in the department will be serially evaluated for sepsis andfollowed up until transplant/death/discharge/90-days. They will be classifiedinto proven-infection, probable-infection, and no-infection groups. The plasmasamples of microbiologically proven infection and no-infection group will besubjected to proteomic analysis by LC/MS. Quantitative and qualitativedescription with pathways of activation will be ascertained between groups.Subgroup analysis will be done between bacterial and fungal infections,survivors and non-survivors, infection as-precipitant and as-complicationgroups, various grades of ACLF, non-infected ACLF and healthy controls. In theverification phase, the top three uniquely expressed protein makers identifiedin the discovery phase will be validated in the baseline samples of the groups.The outcomes will identify the unique biomarkers of sepsis in ACLF,fungal/bacterial infections and non-survivors in ACLF. It will also decipherthe pathophysiology of sepsis in ACLF and help design diagnostic, prognosticand personalized treatment strategies in these patients.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 100

Inclusion Criteria

ACLF patients: i.
Age 18-80 years ii.
Giving a positive consent.

Exclusion Criteria

Patients with i.
Human immunodeficiency virus infection ii.
Pregnancy, iii.
Previous liver or other organ transplantation iv.
Known immunosuppressed states (steroid use in previous 6 months) and v.
Those refusing to give consent will be excluded.

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To compare the clinical and plasma proteomic profile between ACLF patients with culture-proven infections (bacterial and/or fungal) and ACLF patients without infections	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months. \| Validation of results in next 3 months. \| Final data analysis 3 months.

Secondary Outcome Measures

Name	Time	Method
To compare clinical and proteomic profile between patients with culture-proven infections as a precipitant for ACLF and culture-proven infections as a complication during the course of ACLF.	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months.
To compare the clinical and plasma proteomic profile between survivors and non-survivors amongst patients with ACLF.	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months.
To validate the proteomic markers identified on primary analysis in the baseline samples of patients with ACLF.	Validation of results from discovery phase during months 17-19.
To compare the proteomic profile between ACLF patients without infection and healthy controls.	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months.
To compare the clinical and plasma proteomic profile between ACLF patients with culture-proven bacterial infections and culture proven fungal infections.	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months.
To compare the proteomic profile between patients with different grades of ACLF.	Recruitment & follow up of patients and simultaneous proteomic analysis for first 16 months.

Trial Locations

Locations (1): PGIMER Chandigarh
🇮🇳
Chandigarh, CHANDIGARH, India
PGIMER Chandigarh
🇮🇳Chandigarh, CHANDIGARH, India
Dr Nipun Verma
Principal investigator
9914208562
nipun29j@gmail.com