Research Article
Recipient Hyperbilirubinemia May Reduce
Ischemia-Reperfusion Injury but Fails to Improve
Outcome in Clinical Liver Transplantation
Mihai Oltean,
1,2
Christian Barrenäs,
2
Paulo Ney Martins,
3
Gustaf Herlenius,
1,2
Bengt Gustafsson,
1,2
Styrbjörn Friman,
1,2
and William Bennet
1,2
1
Te Transplant Institute, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
2
Sahlgrenska Academy, Te University of Gothenburg, Gothenburg, Sweden
3
Department of Surgery, Transplant Division, University of Massachusetts, Worcester, MA 01655, USA
Correspondence should be addressed to Mihai Oltean; mihai.oltean@surgery.gu.se
Received 2 February 2016; Accepted 24 April 2016
Academic Editor: Edna F. S. Montero
Copyright © 2016 Mihai Oltean et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We
studied if early graf exposure to high bilirubin levels in the recipient afects the early IRI and outcomes afer liver transplantation
(LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identifed a cutofof 2.04 mg/dL for the
recipient pretransplant bilirubin. Recipients were grouped as having low (group L, = 152) or high (group H, = 275) bilirubin.
Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results.
Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day
2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the frst two days afer
transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did
not afect the risk for early graf dysfunction (EGD), death, or graf loss during the frst year afer transplantation nor the incidence
of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin
appears to reduce the early IRI afer LTx yet this improvement was insufcient to improve the clinical outcome.
1. Introduction
Ischemia-reperfusion injury (IRI) of the liver graf reemerges
as a major issue as the pressure of ever increasing waiting
lists requires the use of extended criteria donor livers with
steatosis, older, and non-heart-beating donors. Tese grafs
are more susceptible to IRI with up to 10% of the procured
livers not being transplanted due to the risk of primary
graf nonfunction or dysfunction and ischemic type cholan-
giopathy [1]. Several protective strategies aimed at inducing
biological protective mechanisms in the graf or recipient
before the injurious chain of events in the graf occurs
(i.e., ischemic or pharmacologic preconditioning) have been
explored both in clinical and in experimental settings [2–
5]. Although promising, many of these approaches rely on
complex protocols or toxic chemicals or are technically
demanding and expensive (machine perfusion). Tis ofen
renders them unpractical and limits their clinical applicabil-
ity.
Bilirubin is a byproduct of heme catabolism occurring
through the heme oxygenase-1 pathway. Bilirubin has been
shown to have potent antioxidant properties [6, 7] and exoge-
nous administration of bilirubin in several models of isolated
organ perfusion has been shown to have a protective efect
against IRI when administered before or during the ischemic
event [8, 9]. Experimental evidence indicates that even a brief
contact with bilirubin is sufcient to confer protection against
IRI [8]. Furthermore, a clinical report suggests a protective
efect of increased endogenous bilirubin against develop-
ment of late graf failure afer kidney transplantation [10].
Although the protective mechanisms were unidentifed, the
protective efect could be due to the reduction of the oxidative
Hindawi Publishing Corporation
Gastroenterology Research and Practice
Volume 2016, Article ID 6964856, 6 pages
http://dx.doi.org/10.1155/2016/6964856