Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture

James H. Tabibian, Mohit Girotra, Hsin Chieh Yeh, Dorry L. Segev, Murat T. Gulsen, Guldane Cengiz-Seval, Vikesh K. Singh, Andrew M. Cameron, Ahmet Gurakar

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Introduction. Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). Material and methods. Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. Results. 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). Conclusions. Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

Original languageEnglish (US)
Pages (from-to)395-401
Number of pages7
JournalAnnals of Hepatology
Volume12
Issue number4
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

Endoscopic Retrograde Cholangiopancreatography
Sirolimus
Cholangiography
Immunosuppression
Pathologic Constriction
Transplants
Liver
Liver Transplantation
Therapeutics
Stents
Medical Records
Regeneration
Multivariate Analysis
Logistic Models
Regression Analysis
Prospective Studies

Keywords

  • Anastomosis
  • Biliary obstruction
  • Biliary tract
  • Cholangitis
  • Endoscopy
  • Liver transplantation
  • Stents

ASJC Scopus subject areas

  • Hepatology

Cite this

Tabibian, J. H., Girotra, M., Yeh, H. C., Segev, D. L., Gulsen, M. T., Cengiz-Seval, G., ... Gurakar, A. (2013). Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture. Annals of Hepatology, 12(4), 395-401.

Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture. / Tabibian, James H.; Girotra, Mohit; Yeh, Hsin Chieh; Segev, Dorry L.; Gulsen, Murat T.; Cengiz-Seval, Guldane; Singh, Vikesh K.; Cameron, Andrew M.; Gurakar, Ahmet.

In: Annals of Hepatology, Vol. 12, No. 4, 07.2013, p. 395-401.

Research output: Contribution to journalReview article

Tabibian, JH, Girotra, M, Yeh, HC, Segev, DL, Gulsen, MT, Cengiz-Seval, G, Singh, VK, Cameron, AM & Gurakar, A 2013, 'Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture', Annals of Hepatology, vol. 12, no. 4, pp. 395-401.
Tabibian, James H. ; Girotra, Mohit ; Yeh, Hsin Chieh ; Segev, Dorry L. ; Gulsen, Murat T. ; Cengiz-Seval, Guldane ; Singh, Vikesh K. ; Cameron, Andrew M. ; Gurakar, Ahmet. / Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture. In: Annals of Hepatology. 2013 ; Vol. 12, No. 4. pp. 395-401.
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title = "Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture",
abstract = "Introduction. Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). Material and methods. Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. Results. 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25{\%}) and 6/100 (6{\%}) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95{\%} CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95{\%} CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95{\%} CI 1.02-1.08; p = 0.038). Conclusions. Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.",
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T1 - Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture

AU - Tabibian, James H.

AU - Girotra, Mohit

AU - Yeh, Hsin Chieh

AU - Segev, Dorry L.

AU - Gulsen, Murat T.

AU - Cengiz-Seval, Guldane

AU - Singh, Vikesh K.

AU - Cameron, Andrew M.

AU - Gurakar, Ahmet

PY - 2013/7

Y1 - 2013/7

N2 - Introduction. Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). Material and methods. Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. Results. 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). Conclusions. Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

AB - Introduction. Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). Material and methods. Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. Results. 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). Conclusions. Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

KW - Anastomosis

KW - Biliary obstruction

KW - Biliary tract

KW - Cholangitis

KW - Endoscopy

KW - Liver transplantation

KW - Stents

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VL - 12

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JO - Annals of Hepatology

JF - Annals of Hepatology

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