Minireviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2020; 26(12): 1273-1285
Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1273
Importance of genetic polymorphisms in liver transplantation outcomes
Tomislav Kelava, Petra Turcic, Antonio Markotic, Ana Ostojic, Dino Sisl, Anna Mrzljak
Tomislav Kelava, Dino Sisl, Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Zagreb 10000, Croatia
Petra Turcic, Department of Pharmacology, Faculty of Pharmacy and Biochemistry of University of Zagreb, Zagreb 10000, Croatia
Antonio Markotic, Center for Clinical Pharmacology, University Clinical Hospital Mostar, Mostar 88000, Bosnia and Herzegovina
Ana Ostojic, Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
Anna Mrzljak, Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Supported by the Croatian Science Foundation grant “The Role of Notch Signalling Pathway in Pathogenesis of Hepatic Fibrosis” , No. UIP-2017-05-1965.
Author contributions: Kelava T and Mrzljak A made contributions to the conception and design of the study, were involved in drafting and revising the manuscript critically; Turcic P, Markotic A, Ostojic A and Sisl D were involved in collecting data and drafting the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Anna Mrzljak, MD, PhD, Associate Professor, Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zajceva 19, Zagreb 10000, Croatia. anna.mrzljak@mef.hr
Received: December 31, 2019
Peer-review started: December 31, 2019
First decision: February 19, 2020
Revised: March 1, 2020
Accepted: March 5, 2020
Article in press: March 5, 2020
Published online: March 28, 2020
Processing time: 88 Days and 1.3 Hours
Abstract

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one center on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.

Keywords: Single nucleotide polymorphisms; Liver transplantation; Acute rejection; Non-alcoholic fatty liver disease; New-onset diabetes mellitus; Hepatocellular carcinoma; Tacrolimus

Core tip: Better stratification of risk before transplantation and/or selection of appropriate donor are crucial to reduce post-transplant complications and improve outcomes. The contribution of genetic risk associated with single nucleotide polymorphisms for the most common complications along with the immunosuppression after liver transplantation is briefly summarized in this review.