Graduation Date

Fall 12-15-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Surinder K. Batra, Ph.D.

Second Advisor

Apar K. Ganti, M.D.

Third Advisor

Lani Zimmerman, Ph.D.

Abstract

Introduction: Acute pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The exact cause of post-ERCP pancreatitis (PEP) is unclear. Regardless of the mechanism that initiates PEP, the pathways of inflammation are similar to other forms of acute pancreatitis and include the activation of various inflammatory cytokines, released from the acinar cells and subsequently from helper T lymphocytes and macrophages. Liver transplants (LTx) patients on immunosuppressive medications have impaired T-cell response and hence decreased ability to generate these cytokines. The aim of this study was to review incidence rates and risk factors of PEP in this LTx subset of patient population compared to non transplant (non-LTx) patients. Methods: Retrospective review of liver transplant database from January 2005 to September 2015 was performed. Liver transplant patients who underwent ERCP in the post-transplant period as part of their usual management were included in the study and compared with non-LTX patients who underwent ERCP. The study was approved by IRB. Electronic medical records were reviewed for any mention of pancreatic-type pain and pancreatic enzyme testing, if any after the ERCP. Diagnosis of Post-ERCP pancreatitis was made on the basis of both clinical and laboratory results as per standard definitions of PEP. Results: During this period, 109 LTx patients underwent 235 ERCP procedures. The data was compared with 348 non-transplant patients (not on any immunosuppression) who underwent total of 536 ERCP procedures. PEP developed in 24 (4.47%) cases in the non-LTx group as compared to 4 (1.7%) cases in the LTx group (p = 0.061, OR 2.70). History of LTx showed trend towards decrease in risk of PEP on univariate analysis (OR 0.36, p = 0.068, 95% CI = 0.12 - 1.07). However, on multivariate analysis only female gender (OR 2.35, P < 0.038, CI 1.04 - 5.28), history of PEP (OR 5.77, P < 0.001, CI 2.01 - 16.55) and pancreatic duct contrast injection (OR 6.20, P < 0.001 CI 2.75 - 13.97) were significantly associated with risk of PEP. Also the severity of pancreatitis was mild in all 4 LTx patients as compared to 21 out of 24 patients (87%) with mild PEP in the non-LTx group (pConclusion:The risk of PEP in liver transplant patients on immunosuppression appears lower than the historical risk. Inhibition of the inflammatory transcriptional factors such as NF-kB and NFAT by the calcineurin inhibitors may be a potential explanation. Further studies are needed targeting calcineurin activation as a therapeutic approach in prevention of PEP.

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