Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Dec 24, 2017; 7(6): 349-358
Published online Dec 24, 2017. doi: 10.5500/wjt.v7.i6.349
Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin
Elizabeth Ann Forrest, Janske Reiling, Geraldine Lipka, Jonathan Fawcett
Elizabeth Ann Forrest, Janske Reiling, Geraldine Lipka, Jonathan Fawcett, Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia
Elizabeth Ann Forrest, Department of Surgery, Gold Coast Hospital and Health Service, Gold Coast, Queensland 4215, Australia
Janske Reiling, Jonathan Fawcett, Faculty of Medicine, the University of Queensland, Brisbane, Queensland 4006, Australia
Janske Reiling, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland 4120, Australia
Janske Reiling, Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, AZ Maastricht 6202, The Netherlands
Janske Reiling, PA Research Foundation, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia
Author contributions: Forrest EA, Reiling J and Fawcett J designed the research; Forrest EA, Reiling J and Lipka G performed the research; Forrest EA and Reiling J analyzed the data; Forrest EA wrote the paper; Reiling J, Lipka G and Fawcett J revised the manuscript prior to submission.
Institutional review board statement: The study was reviewed and approved by the Princess Alexandra Hospital (HREC/13/QPAH/382) and University of Queensland (UQ: 2015001248) Human Research Ethics Committee.
Informed consent statement: Approval was obtained from the Queensland Government to access confidential patient information, held by Queensland Health, for the Purpose of Research under the provision of section 280 of the Public Health Act 2005.
Conflict-of-interest statement: The authors of this study have no conflict of interests to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Elizabeth Ann Forrest, MD, BSc BA, Resident Medical Officer, Department of Surgery, Gold Coast Hospital and Health Service, 1 Hospital Boulevard, Southport, Gold Coast, Queensland 4215, Australia. elizabeth.forrest3@health.qld.gov.au
Telephone: +61-7-56870000 Fax: +61-7-56870098
Received: August 13, 2017
Peer-review started: August 14, 2017
First decision: September 4, 2017
Revised: September 18, 2017
Accepted: November 1, 2017
Article in press: November 2, 2017
Published online: December 24, 2017
Processing time: 131 Days and 0.6 Hours
ARTICLE HIGHLIGHTS
Research background

Liver transplantation is a lifesaving surgical procedure available to those eligible with end-stage liver failure. Biliary strictures can cause a disruption in the flow of bile and formation post liver transplantation is a frequent cause for patient morbidity and mortality. Due to the significant burden of disease biliary strictures cause, those patients with biliary strictures often require either endoscopic intervention, surgical re-do of the anastomosis or even re-transplantation.

Research motivation

Biliary strictures post liver transplantation can be classified into two categories, non-anastomotic stricture and anastomotic stricture. Non-anastomotic strictures are often difficult to treat. They are associated with worse outcomes as they often present in numbers and are situated anatomically in a difficult to access location outside the biliary tree. Earlier identification and subsequent treatment of biliary strictures post liver transplant have been associated with improved patient outcomes and decrease the need for re-transplant. Current identified risk factors for biliary stricture formation post liver transplant include sub-optimal surgical technique, the presence of bile leak, hepatic artery thrombosis, primary sclerosing cholangitis, donation after circulatory death donors and prolonged cold or warm ischemic time. Identifying risk factors and clinical indicators for the development of biliary strictures would allow clinicians to identify at risk patients and potentially predict stricture formation. This would allow for earlier treatment of strictures, improving clinical patient care and allograft survival.

Research objectives

This study investigates the risk factors and clinical indicators associated with biliary stricture formation post liver transplantation. In order to translate these findings clinically, this study also aimed to describe potential surveillances method for biliary strictures formation post liver transplantation. These clinical tools would allow for the early identification and treatment of biliary strictures, with the aim of improving patient outcomes.

Research methods

Electronic data for this study was collected retrospectively on all liver donors and recipients in the state of Queensland between 2005 and 2014. Within this data set we analyzed demographic, intra-operative and post-operative characteristics of each procedure. In addition, post-operative liver function tests, serum bilirubin and Tacrolimus levels were collected from post-operative Days 0 to 7. Biliary stricture formation post-operatively was recorded, the interventions used to treat and their timing was also identified. This study was unique in that is used logistical regression to identify potential risk factors and clinical indicators for biliary stricture formation.

Research results

This study demonstrated the incidence of biliary strictures post liver transplantation at our center at 15%. Significant risk factors for the formation of biliary strictures post-transplant included primary sclerosing cholangitis as the primary indication for transplant and the presence of hepatic artery thrombosis. As a clinical indicator, Day 7 total serum bilirubin > 55 μmol/L was found to be associated with an increased risk of stricture formation. Investigation into potential mechanisms explaining this rise in bilirubin in patients with strictures would be beneficial.

Research conclusions

As well as known risk factors for biliary stricture formation, this study identified Day 7 total serum bilirubin > 55 μmol/L as a significant clinical indicator for the development of biliary strictures post liver transplant. As biliary strictures pose a significant burden of morbidity and mortality on patients post liver transplantation, identifying clinical indicators such as elevated total serum bilirubin for stricture formation is a useful tool to enable clinicians to provide early and more successful care to those transplant recipients more at risk. This study identified previously known risk factors for biliary stricture formation post transplantation including primary sclerosing cholangitis are the primary indication for transplant and the presence of hepatic artery thrombosis. Previous studies have identified elevated bilirubin in the post-operative period as a risk factor for biliary stricture formation. This study adds to this body of evidence as it proposes a specific measure of total serum bilirubin (> 55 μmol/L) that is associated with biliary stricture formation post liver transplant. The results of this study can be translated into clinical practice by applying a clinical algorithm to patients that are considered at higher risk of biliary stricture formation post-transplant. The authors suggest focused surveillance of these patients for biliary stricture formation within the immediate three to six-month post-operative period with a magnetic resonance cholangiopancreatography scan.