Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4939
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
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.
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.
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.
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.
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.
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.
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.