Biliary Strictures After Liver Transplantation: Risk Factors and
Prevention by Donor Treatment With Epoprostenol
J. Pirenne, D. Monbaliu, R. Aerts, B. Desschans, Q. Liu, D. Cassiman, W. Laleman, C. Verslype,
M. Magdy, W. Van Steenbergen, and F. Nevens
ABSTRACT
Biliary strictures (BS), a major complication after orthotopic liver transplantation (OLT),
cause morbidity, mortality, graft loss, and increased costs. The virtually unchanged
incidence of BS (approximately 10%–25%) suggests that they are not simply “technical” in
origin, but probably represent a mucosa ischemic injury inherent in the transplantation
procedure. To study risk factors for BS, we analyzed 403 OLTs performed between
January 1, 1997 and December 31, 2006, at a single center, excluding cases of regraft or
death within 1 month. The average time to the diagnosis of the BS was 253 days (range,
7–1002 days). Upon univariate analysis, the absence of flushing of donor bile ducts, an
imported versus a locally procured liver, and rejection were risk factors for BS. In contrast,
the following factors were protective: donor cardiac arrest followed by resuscitation
(suggesting an ischemic preconditioning effect) as well as addition of epoprostenol to and
pressurization of the preservation solution. Patients with higher postoperative peak values
of transaminases, bilirubin, alkaline phosphatase, and gamma glutamyl transpeptidase
were at greater risk for later development of BS. Donor hypotension, donor age, donor
intensive care unit (ICU) stay, type of preservation, positive cross-match, cold and warm
ischemia times, sequential versus simultaneous portal/arterial reperfusion, as well as
cytomegalovirus (CMV) infection were not risk factors for BS. Upon multivariate analysis,
only epoprostenol and pressurization offered protection from BS. In conclusion, this study
2 novel points: (1) patients with high(er) transaminase values and cholestasis early
postoperatively are at greater risk to develop later BS and require close monitoring and (2)
donor maneuvers for better flushing and preserving peribiliary vascular plexus and biliary
mucosa (epoprostenol and pressurization of preservation solution) offer protection from
BS.
T
HE RESULTS OF orthotopic liver transplantation
(OLT) have remarkably improved over the last three
decades. On average, an 80% 1-year survival can be
achieved; experienced centers may reach 90% 1-year sur-
vival.
1
(Fig 1). Despite the improved results, the incidence
of biliary strictures (BS) has remained virtually unchanged,
namely, between 10% and 25%. This observation suggests
that BS are not simply “technical” in origin, but probably
reflect an ischemic and/or a preservation injury to the
biliary mucosa that is inherent to the transplantation pro-
cedure itself.
2,3
It is generally accepted that BS result from
an insult to the peribiliary vascular plexus due to several
factors—immune, toxic, and ischemic—acting separately or
in concert.
1–3
The viscosity of the preservation solution has
also been found to play a role in the pathogenesis of BS.
This effect probably occurs due to suboptimal flushing of
the peribiliary plexus with subsequent suboptimal preserva-
tion of the biliary tree
4
(Fig 2). The aim of the current study
was to reevaluate the risk factors for BS after OLT in order
to reduce their incidence.
From the Liver Transplant Program, University Hospitals Leu-
ven, Leuven, Belgium.
Address reprint requests to Jacques Pirenne, MD, PhD, De-
partment of Abdominal Transplant Surgery, University Hospitals
Leuven, Herestraat 49, 3000 Leuven, Belgium. E-mail: jacques.
pirenne@uzleuven.be
© 2009 Published by Elsevier Inc. 0041-1345/09/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2009.09.026
Transplantation Proceedings, 41, 3399 –3402 (2009) 3399