Inflammatory conditions play a role in recurrence of PSC after liver transplantation: An international multicentre study
Thijmen Visseren,
Nicole S. Erler,
Julie K. Heimbach,
John E. Eaton,
Nazia Selzner,
Aliya Gulamhusein,
Frans van der Heide,
Robert J. Porte,
Bart van Hoek,
Ian P.J. Alwayn,
Herold J. Metselaar,
Jan N.M. IJzermans,
Sarwa Darwish Murad
Affiliations
Thijmen Visseren
Erasmus MC Transplant Institute, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreaticobiliary and Transplant Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Nicole S. Erler
Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Julie K. Heimbach
Department of Surgery, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
John E. Eaton
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
Nazia Selzner
Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
Aliya Gulamhusein
Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
Frans van der Heide
Department of Gastroenterology and Hepatology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands
Robert J. Porte
HPB and Liver Transplant Surgery, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands
Bart van Hoek
LUMC Transplant Center, Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
Ian P.J. Alwayn
Department of General Surgery, Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada; LUMC Transplant Center, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Herold J. Metselaar
Erasmus MC Transplant Institute, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Jan N.M. IJzermans
Erasmus MC Transplant Institute, Department of Surgery, Division of Hepatopancreaticobiliary and Transplant Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
Sarwa Darwish Murad
Erasmus MC Transplant Institute, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Corresponding author. Address: Erasmus MC University Medical Center Rotterdam, Department of Gastroenterology and Hepatology, Office NA-605, Post Office NA-606, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel./Fax: +31-10-703-5942.
Background & Aims: Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries. Methods: In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29–10.11) years post-LT. Results: In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5–5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08–2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC. Conclusions: An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC. Impact and implications: Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.
