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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

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.

Key words. Liver transplantation, Biliary tract, Stents, Anastomosis, Biliary obstruction, Cholangitis, Endoscopy

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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