Role of Fecal Microbiota in Predicting Graft Rejection and Sepsis Among Recipients of Living Donor Liver Transplant in First Year.

NCT04621812 | Unknown

• 1 other identifier: ILBS-FMT-02
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Efficient immunosuppressive therapy and improved surgical techniques have developed liver transplantation as a well-established and life-saving treatment. The 1-year survival rate of approximately 85-90%. Acute cellular rejection (ACR) is one of the main causes of liver dysfunction (LD) after liver trans- plantation, occurring 30% to 70% of transplanted patients and potentially leading to allograft failure. In addition to ACR, presence of sepsis, drug injury, viral infections like CMV or recurrence of viral hepatitis is also other causes of graft dysfunction. Laboratory tests are commonly used as less invasive methods of monitoring allograft rejection, but they are not specific to rejection and are often elevated in other types of graft dysfunction too. Till date the immunosuppressive regimen in liver transplant recipient is considered as an art in absence of an objective measures of the immune state. Therapeutic drug monitoring has little value in the assessment of the immune state and is always used as a supportive guide. The development of specific immune monitoring assays to measure the net immunosuppressive state in a transplant recipient would allow a more individualized therapeutic regimen Patients with altered gut microbiota had more chances of infection and longer course of hospital stay. Probiotics could mediate beneficial effects in graft rejection. Dysbiosis activates T cells through PAMPS and causes the inflammatory injury in the graft liver. The studies shown that lower Eubacteria, Bifidobacterium, Faecal bacterium and Lactobacillus with abundance of Enterococcus and Enterobacteriaceae. They restored to near normal after transplant in majority. This is known that there is a dysbiosis in the natural history of ACLF or decompensated cirrhosis, and often correlated to complications like-endotoxemia, sepsis, worsening liver failure and poor survival. This has led to consider fecal microbiota modulation as an emerging therapy. Liver transplant and consequent recovery, there is over all change in the recipient homeostatic milieu as well as the immune milieu and the same may be happening to the gut flora too.It's well known that liver has animprint of resident gut flora. The preliminary rat model showed alteration of gut flora to predict the development acute cellular rejection before it happens. Similarly the risk of infection is more among transplant recipients with decreased microbial diversity after liver transplant. However the data is scanty and there is an urgent need to understand the mechanism.. The present study was necessitated in view of emerging role of gut microflora and its influence on immune remodeling for the prediction of infection, rejection and may be an early biomarker for the graft dysfunction. This may be of varied cause in liver transplant recipients along with its impact on overall immune status. Uniqueness of the present study will be to understand the mechanism of development of sepsis or graft dysfunction in due course of time using high-throughput tools of single cell analysis in whole blood and gut microbiota alterations among liver transplant recipient as a cause for graft dysfunction in first year of live donor liver transplant.

Conditions

Acute Liver Failure; Acute-On-Chronic Liver Failure; Liver Cirrhosis

Outcome Measures

Primary Outcomes (4)

• Development of sepsis

  Sepsis diagnosis is based on positive cultures of the patient (Blood, urine, tip of catheter ), foci of infection by cross sectional imaging at any point of time

  1 years

• Development of rejection

  Rejection dosgnosis is based on graft biopsy and histology - assessed by REJECTION ACTIVITY INDEX (RAI)

  1 years

• Development of CMV infection

  CMV DNA diagnosis is by RT PCR technique

  1 years

• Death

  1 years

Secondary Outcomes (2)

• Post LT complications requiring surgical interventions

  1 years

• Number of patients who will undergo Retransplantation

  1 years

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive 100 patients fulfilling the eligibility criteria and undergoing living donor liver transplant in ILBS between April 2020 to March 2022.

You may qualify if:

• Living donor Liver transplantation for ALF, ACLF, cirrhosis and its complications.
• Age 12-75 years
• Valid consent

You may not qualify if:

• Deceased Donor Liver Transplants
• Re-transplants
• Simultaneous Liver-Kidney Transplants (SLKT)

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

RECRUITING

MeSH Terms

Conditions

Liver Failure, Acute; Acute-On-Chronic Liver Failure; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr Navin Kumar M, MD

CONTACT

01146300000; navinktanvi10@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: November 9, 2020
• Study Start: November 8, 2020
• Primary Completion: October 10, 2022
• Study Completion: October 10, 2022
• Last Updated: October 5, 2021

Record last verified: 2021-10

Locations

IN (1)