P478. Increased activity of inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis
K.K. Jørgensen1, L. Lindström2, M. Cvancarova3, T.H. Karlsen1, M. Castedal4, S. Friman4, E. Schrumpf1, A. Foss5, H. Isoniemi6, A. Nordin6, K. Holte7, A. Rasmussen7, A. Bergquist2, M.H. Vatn1, K.M. Boberg1, 1Oslo University Hospital, Rikshospitalet, Section for Gastroenterology, Oslo, Norway, 2Karolinska University Hospital, Department of Gastroenterology and Hepatology, Stockholm, Sweden, 3University of Oslo, Department of Biostatistics, Oslo, Norway, 4Sahlgrenska University Hospital, The Transplant Institute, Gothenburg, Sweden, 5Oslo University Hospital, Rikshospitalet, Section for Transplantation Surgery, Oslo, Norway, 6Helsinki University Hospital, Transplantation and Liver Surgery Clinic, Helsinki, Finland, 7University of Copenhagen, Rigshospitalet, Department of Surgical Gastroenterology and Liver Transplantation, Copenhagen, Denmark
Background
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease, strongly associated with inflammatory bowel disease (IBD) and a major cause of liver transplantation (Ltx) in the Nordic countries. Previous studies have shown highly variable results regarding the course of IBD after Ltx. We aimed to describe the natural history of IBD in liver transplanted PSC patients and to identify potential risk factors for increased disease activity post Ltx.
Methods
In a longitudinal, multicenter study within the Nordic Liver Transplant Group, we included PSC patients who had undergone Ltx from 1984 to 2007. The clinical activity of IBD before and after Ltx was compared and the effect of medication and other factors on the course of IBD post Ltx was analysed.
Results
Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 11 (2.5%) patients developed de novo IBD post Ltx. The median duration of IBD was 15 (0–50) years at the time of Ltx and follow-up after Ltx was 5 (0.5–20) years. Macroscopic inflammation was more frequent after compared to before Ltx (p < 0.001) (Figure 1). The degree of inflammation after Ltx was increased in 88 (40%), unchanged in 93 (43%) and decreased in 37 (17%) patients (Figure 1). The relapse rate after Ltx was higher than that before (p < 0.001). The overall clinical IBD activity was also increased after Ltx (p < 0.001). The cumulative risk of colectomy due to active disease after Ltx was increased compared to the corresponding risk before Ltx, although not reaching statistical significance (HR 1.4, p = 0.22). Young age at diagnosis of IBD and dual treatment with tacrolimus and mycophenolate mofetil (MMF) were significant risk factors for increased IBD activity post Ltx, whereas combination treatment with ciclosporine A (CsA) and azathioprine showed a protective effect (Table 1).
Figure 1. Frequency and severity of IBD activity in PSC patients (n = 218) before and after liver transplantation.
| Variable | Variable present | Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|---|---|
| yes/no (n) | HR | 95% CI | p-value | HR | 95% CI | p-value | |
| Age <20 years at diagnosis of IBD | 62/156 | 1.7 | 1.1–2.6 | 0.027 | 1.8 | 1.1–2.9 | 0.011 |
| Tacrolimus* | 71/147 | 1.6 | 1.0–2.6 | 0.050 | 1.9 | 0.9–3.7 | 0.067 |
| Tacrolimus + MMF* | 65/153 | 3.5 | 2.1–5.8 | <0.001 | 3.9 | 1.9–7.9 | 0.001 |
| Ciclosporine A* | 20/198 | 0.8 | 0.4–1.3 | 0.265 | |||
| Ciclosporine A + azathioprine* | 50/168 | 0.2 | 0.1–0.5 | <0.001 | 0.4 | 0.2–0.9 | 0.043 |
| Aminosalicylates* | 83/135 | 1.0 | 0.7–1.7 | 0.862 | |||
| Steroid treated rejection# | 125/93 | 1.0 | 0.7–1.6 | 0.949 | |||
| ATG/OKT3 treated rejection# | 30/188 | 0.6 | 0.3–1.0 | 0.061 | |||
| Treated CMV-infection# | 47/171 | 0.9 | 0.5–1.5 | 0.600 | |||
| *Used for minimum three months during the first six months after Ltx. #Treatment during the first six months after Ltx. | |||||||
Conclusion
The activity of IBD in PSC increases after Ltx and appears to be influenced by the immunosuppression given. In PSC patients undergoing Ltx, a shift from present standard maintenance treatment with tacrolimus and MMF to CsA and azathioprine should be considered.