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

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.