Microbiota-directed intervention in living donor liver transplant recipients: protocol for a randomised double-blind placebo-controlled trial.

introductionAcute-on-chronic liver failure (ACLF) patients have the highest propensity for post-liver transplantation (LT) infections and mortality. Liver-associated diseases have been one of the primary targets for synbiotic therapy to augment immunity and mitigate infections. However, despite multiple studies showing benefits of synbiotics in liver diseases, data on their use following LT are sparse. METHODS AND ANALYSIS: This randomised placebo-controlled study aims to assess the impact of synbiotics in ACLF patients undergoing living donor liver transplantation (LDLT). Following randomisation by computer-generated block number sequence, 3 days prior to LDLT, the intervention arm will receive standard medical treatment and synbiotics (VSL#3 a probiotic, and Yogut, prebiotic and probiotic combination) for 6 weeks, while the control arm will receive standard medical treatment with a placebo. The patients will be followed up for 6 months to study the clinical and biochemical outcomes. The primary objective is to compare the difference in the occurrence of infectious complications between the patients who receive synbiotics versus placebo during the 6-month period following LDLT. The secondary objectives include assessing the qualitative and quantitative change in microbiota with synbiotics and LDLT, adverse reactions due to synbiotics, and post-LT morbidity and mortality. The minimum sample size comes to 71 in each group. The first 50 patients in the study protocol will undergo gut microbiome analysis using 16s metagenomic and nanopore sequencing to analyse the microbial composition before starting synbiotics/placebo and at 6 weeks after LDLT. ETHICS AND DISSEMINATION: The study is approved by the Research Ethics Committee of Amrita Institute of Medical Sciences, Kochi, India (IEC-AIMS-2022-GISUR-203) and registered in the Clinical Trial Registry of India (CTRI) CTRI/2022/10/046327. The results of the trial will be disseminated by presentation at national/international conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046327 - Clinical Trial Registry of India.