Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 28, 2016; 8(3): 148-161
Published online Jan 28, 2016. doi: 10.4254/wjh.v8.i3.148
Management of immunosuppressant agents following liver transplantation: Less is more
Mustafa S Ascha, Mona L Ascha, Ibrahim A Hanouneh
Mustafa S Ascha, Mona L Ascha, Ibrahim A Hanouneh, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, United States
Author contributions: Ascha MS participated in writing and critical revision of the manuscript for important intellectual content and final approval of the manuscript submitted; Ascha ML participated in critical revision of the manuscript for important intellectual content and final approval of the manuscript submitted; Hanouneh IA participated in critical revision of the manuscript for important intellectual content and final approval of the manuscript submitted.
Conflict-of-interest statement: All of the authors have no significant conflicts of interest with any companies or organization whose products or services may be discussed in this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ibrahim A Hanouneh, MD, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States. hanouni2@ccf.org
Telephone: +1-216-4441762 Fax: +1-216-4446302
Received: July 1, 2015
Peer-review started: July 1, 2015
First decision: August 31, 2015
Revised: December 13, 2015
Accepted: January 5, 2016
Article in press: January 7, 2016
Published online: January 28, 2016
Abstract

Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.

Keywords: Immunosuppression, Orthotopic liver transplantation, Metabolic syndrome, Acute cellular rejection, Hepatitis C virus

Core tip: The use of immunosuppressive agents is reviewed in the context of the modern post-orthotopic liver transplantation population. The side effects of mainstay immunosuppressive strategies exacerbate some patient pathologies, and combinations of different immunosuppressants could be more specifically tailored to patient needs. Acute cellular rejection and malignant complications are also discussed with respect to immunosuppressive strategies. Finally, hepatitis C virus and its impact on immunosuppression is re-evaluated in light of recent developments in viral clearance.