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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lukas Bajer, MD, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 140 21, Czech Republic.
lukas.bajer@ikem.cz
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
Processing time: 82 Days and 7.9 Hours
AIM
To evaluate risk factors for primary sclerosing cholangitis (PSC) recurrence (rPSC) after orthotopic liver transplantation (OLT) in patients with well-preserved colons.
METHODS
We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with follow-up of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen (HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.
RESULTS
Altogether, 31 men and 16 women with a median (range) age of 36 (15-68) years at the time of OLT and a median follow-up of 122 (60-249) mo were included. rPSC was confirmed in 21/47 (44.7%) of patients, a median 63 (12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio (HR): 4.02, 95% confidence interval (CI): 1.58-10.98] and history of acute cellular rejection (rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis (rPSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor (rPSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04 (rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03 (rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07 (rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.
CONCLUSION
De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.
Core tip: This study demonstrates that patients with de novo colitis after liver transplantation for primary sclerosing cholangitis (PSC) are significantly predisposed towards primary liver disease recurrence (rPSC). History of acute cellular rejection of the liver graft, overlapping features of autoimmune hepatitis (autoimmune hepatitis /PSC) and certain human leukocyte antigen (HLA)-DQ and HLA-DR alleles in both donors and recipients may also have an impact on rPSC development. These data based on analysis of well-defined cohort with long median follow-up suggest that thorough routine endoscopic, radiological and immunological examination (both pre- and post-transplant) is crucial for identifying high-risk patients.
