Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

Abstract

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.

Keywords: Acute cellular rejection; Autoimmune hepatitis; Human leukocyte antigen; Immunosuppression; Inflammatory bowel disease; Liver transplantation; Primary sclerosing cholangitis.

Figure 1

Study design, exclusion criteria, and the study cohort. OLT: orthotopic liver transplantation; CMV: Cytomegalovirus.

Figure 2

Kaplan-Meier plots of patient (A) and graft (B) survival in the total population, and graft survival in the study cohort (C).

Figure 3

Kaplan-Meier plots of recurrent primary sclerosing cholangitis-free survival in patients with pre-orthotopic liver transplantation inflammatory bowel disease (blue line) and de novo inflammatory bowel disease (red line).

Figure 4

Distribution of time to recurrent primary sclerosing cholangitis in patients with cyclosporine immunosuppression (red line) vs tacrolimus immunosuppression (blue line).