Natural History of Established and de Novo Inflammatory Bowel Disease after Liver Transplantation for Primary Sclerosing Cholangitis

Edward Vincent Loftus, Jr, Mohamad A. Mouchli, Siddharth Singh, Lisa Allyn Boardman, David H. Bruining, Amy Lightner, Charles B. Rosen, Julie K. Heimbach, Bashar Hasan, John J. Poterucha, Kymberly D. Watt, Sunanda V. Kane, Laura E. H. Raffals

Research output: Contribution to journalArticle

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Abstract

Background The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. Methods In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. Results Three hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. Conclusions The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096-video1 izx096.video1 5746673864001.

Original languageEnglish (US)
Pages (from-to)1074-1081
Number of pages8
JournalInflammatory Bowel Diseases
Volume24
Issue number5
DOIs
StatePublished - Apr 23 2018

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Sclerosing Cholangitis
Natural History
Inflammatory Bowel Diseases
Liver Transplantation
Immunosuppression
Azathioprine
Mycophenolic Acid
Transplants
Colectomy
Tacrolimus

Keywords

  • inflammatory bowel disease
  • liver tranpslant
  • primary sclerosing cholangitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Natural History of Established and de Novo Inflammatory Bowel Disease after Liver Transplantation for Primary Sclerosing Cholangitis. / Loftus, Jr, Edward Vincent; Mouchli, Mohamad A.; Singh, Siddharth; Boardman, Lisa Allyn; Bruining, David H.; Lightner, Amy; Rosen, Charles B.; Heimbach, Julie K.; Hasan, Bashar; Poterucha, John J.; Watt, Kymberly D.; Kane, Sunanda V.; Raffals, Laura E. H.

In: Inflammatory Bowel Diseases, Vol. 24, No. 5, 23.04.2018, p. 1074-1081.

Research output: Contribution to journalArticle

Loftus, Jr, EV, Mouchli, MA, Singh, S, Boardman, LA, Bruining, DH, Lightner, A, Rosen, CB, Heimbach, JK, Hasan, B, Poterucha, JJ, Watt, KD, Kane, SV & Raffals, LEH 2018, 'Natural History of Established and de Novo Inflammatory Bowel Disease after Liver Transplantation for Primary Sclerosing Cholangitis', Inflammatory Bowel Diseases, vol. 24, no. 5, pp. 1074-1081. https://doi.org/10.1093/ibd/izx096
Loftus, Jr, Edward Vincent ; Mouchli, Mohamad A. ; Singh, Siddharth ; Boardman, Lisa Allyn ; Bruining, David H. ; Lightner, Amy ; Rosen, Charles B. ; Heimbach, Julie K. ; Hasan, Bashar ; Poterucha, John J. ; Watt, Kymberly D. ; Kane, Sunanda V. ; Raffals, Laura E. H. / Natural History of Established and de Novo Inflammatory Bowel Disease after Liver Transplantation for Primary Sclerosing Cholangitis. In: Inflammatory Bowel Diseases. 2018 ; Vol. 24, No. 5. pp. 1074-1081.
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abstract = "Background The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. Methods In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. Results Three hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9{\%} male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1{\%}) required escalation of therapy, whereas 87 had a stable course (57.6{\%}) and 8 patients (5.3{\%}) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0{\%}, 18.5{\%}, and 25.5{\%}, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2{\%}) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5{\%}, 20.0{\%}, and 25.4{\%}, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. Conclusions The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5{\%}, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4{\%}. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096-video1 izx096.video1 5746673864001.",
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T1 - Natural History of Established and de Novo Inflammatory Bowel Disease after Liver Transplantation for Primary Sclerosing Cholangitis

AU - Loftus, Jr, Edward Vincent

AU - Mouchli, Mohamad A.

AU - Singh, Siddharth

AU - Boardman, Lisa Allyn

AU - Bruining, David H.

AU - Lightner, Amy

AU - Rosen, Charles B.

AU - Heimbach, Julie K.

AU - Hasan, Bashar

AU - Poterucha, John J.

AU - Watt, Kymberly D.

AU - Kane, Sunanda V.

AU - Raffals, Laura E. H.

PY - 2018/4/23

Y1 - 2018/4/23

N2 - Background The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. Methods In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. Results Three hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. Conclusions The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096-video1 izx096.video1 5746673864001.

AB - Background The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. Methods In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. Results Three hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. Conclusions The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096-video1 izx096.video1 5746673864001.

KW - inflammatory bowel disease

KW - liver tranpslant

KW - primary sclerosing cholangitis

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