Current state of clinical trials regarding liver transplant rejection

• Published in: Transplant immunology 2022-02, Vol.70, p.101522-101522, Article 101522
• Main Authors: El Masri, Jad, El Ayoubi, Lemir Majed, Zreika, Bachir, Adhami, Fouad, El Masri, Diala, El Hage, Said, Abou-Jaoudé, Maroun
• Format: Article
• Language: English
• Subjects: Clinical trials; Graft Rejection - drug therapy; Humans; Immunosuppression Therapy; Immunosuppressive Agents - therapeutic use; Liver; Liver Transplantation; Sirolimus - therapeutic use; Therapy; Transplant rejection
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2021.101522

Liver transplant (LT) is the second most common transplant intervention. The rate of acute cellular rejection (ACR) is 15–25% after LT, while being higher in chronic rejection (CR). Clinical trials had a major role in getting more potent and selective immunosuppressive medications. Our study plays an important role by evaluating and tracking clinical trials related to liver transplant rejection, focusing on interventional therapeutic trials. On October 28, we searched Clinicaltrials.gov for interventional clinical trials related to liver transplant rejection. A total of 27 clinical trials included in this study. Characteristics on each trial were collected, and availability of linked publications was searched using Medline/PubMed and Embase/Scopus. Content of publications was reviewed and main findings were summarized. Majority of trials were completed (15 out of 27). Eleven trials had between 11 and 50 participants, and 10 had above 100. The study duration was between 1 and 4 years for the majority of trials (16 trials), with an average of 3.77 years. Most of the trials were done in Europe/UK/Russia (n = 12). The results were provided in 9 trials but published in 4, showing the possible tolerogenic efficacy of MSC in liver transplantation, increased success of immunosuppression (IS) withdrawal after sirolimus addition, efficacy of Alemtuzumab, normal graft function and stability within 1 year of immunosuppression withdrawal. This study revealed a low number of trials, lack of variety in location and low publishing rates. The focus of trials was mainly towards side effects and safety of immunosuppressants, and their withdrawal. These trials reached results that must be built on to reach definitive guidelines and treatment strategies. This highlights the need for better management of human and financial resources, in order to reach new and more effective therapeutic strategies, leading to the decrease in rate of LTR. •Regarding Liver transplant rejection, there is low number of trials, lack of variety in location and low publishing rates.•Clinical trials were distributed as: 30% phase IV, 26% not specified, and 22% phase 2, with a total of 2492 participants.•Focus of trials was not towards prevention of rejection, as much as side effects and safety.•Several clinical trials targeted the idea of increasing tolerance with decreasing immunosuppression, so mainly targeting “withdrawal”.