Publication

Abstract : Acute cellular rejection remains a significant challenge, affecting 10-40% of liver transplant recipients despite advancements in immunosuppressive therapies. While liver biopsy is the gold standard for diagnosing rejection, it is invasive, costly, and associated with potential complications. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising noninvasive biomarker, providing real-time insights into graft health through simple blood sampling. This randomized controlled trial aims to evaluate the efficacy of dd-cfDNA-modulated immunosuppression in reducing acute T-cell-mediated rejection. Participants undergoing live donor liver transplantation will be randomized into two groups. The intervention group will have dd-cfDNA levels monitored on postoperative days 3, 7, 14, 30, and 90, with elevated levels prompting adjustments in immunosuppressive therapy. The control group will follow standard liver function test (LFT)- based protocols. Both groups will undergo liver biopsy only if significant LFT abnormalities are observed. The primary outcome is the incidence of biopsy-proven rejection. Secondary outcomes include the effectiveness of dd-cfDNA for early rejection detection compared to LFTs and an assessment of graft integrity at one year. Additional analyses will explore correlations between dd-cfDNA levels, T-cell markers, and rejection subtypes. This trial hypothesizes that dd-cfDNA monitoring can reduce rejection rates and minimize the need for invasive biopsies, ultimately improving patient outcomes. With no added risk as only routine follow-up blood samples are required, this study offers a potential paradigm shift in noninvasive, personalized post-transplant rejection management. Clinical Trial Registry- India (CTRI)- CTRI/2025/01/097936 Registered on: 19/02/2025 https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIyNDI0&Enc=&userName=CTRI/2025/02/080893