title: Sirolimus may be associated with early recurrence of biliary obstruction in liver transplant patients undergoing endoscopic stenting of biliary strictures.
abstract: BACKGROUND
  Recurrent biliary obstruction necessitating premature repeat endoscopic retrograde pancreatography (ERCP) remains a costly and morbid problem in patients undergoing treatment of post-orthotopic liver transplantation (OLT) biliary strictures. We evaluated the relationship between prednisone or sirolimus use and early recurrence of biliary obstruction given their negative effects on collagen production and cholangiocyte regeneration.
  
  
  METHODS
  Medical records of adult patients who underwent OLT from 1998-2008 and developed anastomotic (ABS) and/or nonanastomotic (NABS) biliary strictures requiring endoscopic plastic stent therapy were reviewed. Outcome was early recurrence of biliary obstruction requiring repeat ERCP. Univariate and multivariable logistic regression analysis, adjusting for age, sex, and time from OLT to ERCP, were performed.
  
  
  RESULTS
  35 patients with ABS and 9 patients with NABS underwent a total of 157 ERCPs. Median patient age was 56 years, 68% were male, and hepatitis C was the most common OLT indication (52%). Early recurrence of biliary obstruction ocurred following 17.1% of ERCPs. In univariate analysis, neither prednisone nor sirolimus was associated with early recurrence of biliary obstruction. In multivariate analysis, however, sirolimus use was associated with increased incidence of early recurrent biliary obstruction (OR = 2.53; 95% CI: 0.77-8.32; p = 0.12); this was more pronounced at doses > 3 (OR = 4.27; 95% CI: 0.62-29.3; p = 0.14) than at ≤ 3 mg/day (OR = 2.24; 95% CI: 0.62-8.13; p = 0.22) and statistically significant in patients with ABS only (OR = 1.44 per mg increase in sirolimus dose; 95% CI 1.02-2.03; p = 0.037).
  
  
  CONCLUSIONS
  Sirolimus use, particularly at higher doses and patients with ABS, may be associated with an increased risk of early recurrence of biliary obstruction requiring repeat ERCP for post-OLT biliary strictures. Additional studies are needed to further investigate these findings and elucidate other risk factors.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. tabibian.james@mayo.edu
authors.forename: James H
authors.initials: JH
authors.lastname: Tabibian
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Yeh
authors.forename: Vikesh K
authors.initials: VK
authors.lastname: Singh
authors.forename: Guldane
authors.initials: G
authors.lastname: Cengiz-Seval
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Cameron
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gurakar
mesh_terms: D000328:Adult; D000368:Aged; D002760:Cholangiopancreatography, Endoscopic Retrograde; D002779:Cholestasis / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D016031:Liver Transplantation / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D015607:Stents; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D011241:Prednisone; D020123:Sirolimus