Current state of clinical trials regarding liver transplant rejection

Jad El Masri; Lemir Majed El Ayoubi; Bachir Zreika; Fouad Adhami; Diala El Masri; Said El Hage; Maroun Abou-Jaoudé

doi:10.1016/j.trim.2021.101522

Current state of clinical trials regarding liver transplant rejection

Transpl Immunol. 2022 Feb:70:101522. doi: 10.1016/j.trim.2021.101522. Epub 2021 Dec 23.

Authors

Jad El Masri¹, Lemir Majed El Ayoubi², Bachir Zreika², Fouad Adhami², Diala El Masri³, Said El Hage⁴, Maroun Abou-Jaoudé⁵

Affiliations

¹ Faculty of Medicine, Lebanese University, Beirut, Lebanon; Faculty of Medicine, Neuroscience Research Center, Lebanese University, Beirut, Lebanon. Electronic address: Jadmasri_1998@hotmail.com.
² Faculty of Medicine, Lebanese University, Beirut, Lebanon.
³ Faculty of Medicine, University of Balamand, Nord, Lebanon.
⁴ Faculty of Medicine, Lebanese University, Beirut, Lebanon; Faculty of Medicine, Neuroscience Research Center, Lebanese University, Beirut, Lebanon; INSPECT-LB (Institut National de Santé Publique, Epidémiologie Clinique et Toxicologie-Liban), Beirut, Lebanon.
⁵ Faculty of Medicine, Lebanese University, Beirut, Lebanon; Department of Surgery, Middle East Institute of Health, Bsalim, Lebanon; Department of Surgery, Saint-George Hospital-UMC, Beirut, Lebanon.

PMID: 34954324
DOI: 10.1016/j.trim.2021.101522

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Clinical trials; Liver; Therapy; Transplant rejection.

MeSH terms

Graft Rejection / drug therapy
Humans
Immunosuppression Therapy
Immunosuppressive Agents / therapeutic use
Liver Transplantation*
Sirolimus / therapeutic use

Substances

Immunosuppressive Agents
Sirolimus