Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2018; 24(43): 4939-4949
Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4939
Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease
Lukas Bajer, Antonij Slavcev, Peter Macinga, Eva Sticova, Jan Brezina, Matej Roder, Radim Janousek, Pavel Trunecka, Julius Spicak, Pavel Drastich
Lukas Bajer, Peter Macinga, Jan Brezina, Pavel Trunecka, Julius Spicak, Pavel Drastich, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
Antonij Slavcev, Matej Roder, Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
Eva Sticova, Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
Radim Janousek, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague 140 21, Czech Republic
Author contributions: All mentioned authors substantially contributed to presented research; Bajer L, Slavcev A, Sticova E and Drastich P wrote the paper; Slavcev A and Roder M performed HLA typing and analysed acquired data; Bajer L, Macinga P and Brezina J gathered and analysed retrospective data; Sticova E reviewed all relevant histological findings; Janousek R reviewed all relevant radiological findings; Trunecka P, Spicak J and Drastich P designed and supervised the research; Spicak J and Drastich P revised the manuscript
Supported by the Ministry of Health of the Czech Republic, No. 15-28064A and No. 16-27477A.
Institutional review board statement: This study was approved by The Ethics Committee with multicenter competence of the Institute for Clinical and Experimental Medicine and Thomayer Hospital.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare that there are no competing interests regarding the publication of this paper.
Data sharing statement: No additional data are available.
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:
Correspondence to: Lukas Bajer, MD, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 140 21, Czech Republic.
Telephone: +420-2-61362266 Fax: +420-2-61362615
Received: August 31, 2018
Peer-review started: September 2, 2018
First decision: October 8, 2018
Revised: October 20, 2018
Accepted: November 13, 2018
Article in press: November 13, 2018
Published online: November 21, 2018
Research background

Recurrence of primary sclerosing cholangitis (rPSC) is the most common cause of liver graft failure in patients after liver transplantation (OLT) for PSC. Many previous studies aimed to identify risk factors associated with rPSC. However, results of these studies were often incoherent or even contradictory. This single-center study describes potential risk factors for rPSC in thoroughly selected cohort of patients with longest median and maximum follow-up presented up-to-date.

Research motivation

Identifying relevant risk factors for rPSC is a cornerstone for proper stratification of PSC patients in both pre-OLT and post-OLT arrangement. In the future, this should lead to establishing tailored examination and therapeutic (e.g., immunosuppression regimens) protocols, especially for high-risk individuals. Such measures could reduce morbidity and mortality in patients with this serious clinical condition.

Research objectives

Principal objective of this study was to determine which clinical features are significantly predisposed towards rPSC development. As there was no other study on the topic previously performed in Central Europe, the aim was to assess the outcomes after over twenty years of experience with liver transplantation in our center. Identification of risk factors for rPSC will surely direct future research in the field of recurrent disease pathogenesis.

Research methods

As this is a study with retrospective design, we analysed all available relevant medical records of patients included in the study while sticking with strict inclusion and exclusion criteria. Standard statistical methods were used to determine significance of obtained results. This included two-tailed Fisher’s exact test, Student’s t-test or the Mann-Whitney U test, analysis by Kaplan-Meier method (with subsequent log-rank test) and Cox proportional hazards regression model.

Research results

The most novel finding of this study is represented by very tight association of rPSC and de novo inflammatory bowel disease after OLT. In accordance with several previous studies, we also demonstrated that patients with history of acute cellular rejection after OLT are also at increased risk of rPSC development, similarly as patients with overlapping features of autoimmune hepatitis pre-OLT. Moreover, several human leukocyte antigen (HLA)-DR and HLA-DQ alleles appeared to be promising markers in assessing the risk of rPSC. To confirm these findings, performing of large-scale prospective study would be highly warranted.

Research conclusions

Despite the fact, that previous studies described association of IBD and rPSC, this is the first study demonstrating that patients with de novo colitis are at significantly higher risk of rPSC as compared to patients with IBD diagnosed pre-OLT. The work also demonstrates that those who experienced ACR after OLT should be under careful surveillance for signs of rPSC. Moreover, presence of several HLA-DR and HLA-DQ alleles in both donors and recipients had a clear tendency to increase or decrease the risk of PSC. Therefore, routine HLA assessment could lead to more careful donor selection or at least to stratifying the patients for the risk of rPSC development. Routine MRCP should be considered in all those transplanted for PSC as rPSC seems to be highly under-diagnosed. High incidence of de novo colitis raises a question regarding more frequent endoscopic evaluation of patients with no previous history of IBD.

Research perspectives

Presented study brings special attention to poorly defined clinical entity of de novo colitis after liver transplantation and its tight relation to PSC recurrence in the liver graft. Future basic and clinical research should define pathogenetic link between both entities and provide diagnostic algorithms and treatment protocols for both these important clinical conditions.