Abstract Background Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications. Case presentation Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae. Conclusion This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.</p

AA Shaked

Aiman Obed

Armin D Goralczyk

BJ Stange

CK Oh

DH Adams

E Hatano

EF Wijdicks

Giuliano Ramadori

JA Goss

JH Silverstein

KD Mullen

M Odeh

P Pandharipande

S Nikeghbalian

S Pastacaldi

S Todo

SK Inouye

SM Riordan

T Ikegami

T Soliman

The Boston Collaborative Drug Surveillance Program

Thomas Lorf

Volker Meier

WM Lee

English

PubMed

Crossref

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

Springer - Publisher Connector

CASE REPORT Open Access
Acute paranoid psychosis as sole clinical
presentation of hepatic artery thrombosis after
living donor liver transplantation
Armin D Goralczyk1*, Volker Meier2, Giuliano Ramadori2, Aiman Obed1, Thomas Lorf1
Abstract
Background: Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often
requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality.
Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be
associated with the advent of surgical complications.
Case presentation: Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation
which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-
transplantation the patient recovered without sequelae.
Conclusion: This case highlights the need to remain cautious when psychiatric disorders occur in patients after
liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of
psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.
Background
Hepatic artery thrombosis (HAT) is the most frequent
arterial complication in orthotopic liver transplantation
(OLT) occurring in 2.5-6.8% of adult transplant recipi-
ents including adult living donor liver transplant recipi-
ents [1-3] with an increased incidence in pediatric and
ABO-incompatible liver transplantation [4,5]. The clini-
cal presentation of HAT varies depending on the time
of onset after transplantation. Severe acidosis, fever, sys-
tematic inflammatory response syndrome, or hepatic
failure may ensue in early HAT (less than one month
after OLT), whereas presentation of late HAT may vary
from biliary complications such as recurrent biliary sep-
sis and stenotic lesions of the biliary tract, to an asymp-
tomatic clinical picture with a mild elevation of serum
transaminases and bilirubin levels [2,6]. HAT may thus
be indicated by elevated serum transaminases, prolonged
prothrombin time, or elevated total bilirubin and may be
confirmed by doppler ultrasonography or angiography.
Although in approximately 47% HAT requires re-OLT,
cases without progressive allograft failure arterial flow
may be resolved by fibrinolysis, interventional treatment,
or surgical thrombectomy [1]. Mortality of HAT may
vary from 55.6% (early HAT) to 15% (late HAT) [2].
The most common cause for HAT is surgical technique
but hemodynamic or immunologic factors, such as
reperfusion injury, hypercoagulation, and viral infections
have also been recognized [1,7]. Risk factors for HAT
include the number of allografts, cytomegalovirus
(CMV) infection status, high recipient/donor weight
ratio, biopsy proven rejection, and combination of
female donor and male recipient [2].
Case presentation
A 42-year-old male patient underwent a living-donor
liver transplantation (LDLT) for progressive hepatitis B,
cirrhosis with 7 points on the Child-Turcotte-Pugh scale
and a model for end-stage liver disease score of 10. He
was placed on the waiting list for transplantation because
of suspected hepatocellular carcinoma. He had no history
of psychiatric disorder. The donor was his 43-year-old
brother who had no major medical problems. The clini-
cal match was appropriate (see Table 1), there were no
contraindications and after further evaluation recipient
and donor were found to be suitable for LDLT.
* Correspondence: agoralczyk@med.uni-goettingen.de
1Department of General and Visceral Surgery, University Medical Center
Göttingen, Göttingen, Germany
Goralczyk et al. BMC Surgery 2010, 10:7
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© 2010 Goralczyk et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
The donor underwent standard right lobectomy with
preservation of the middle vein. In the recipient a stan-
dard total hepatectomy was performed, but due to suc-
cessive intimal dissection of the hepatic and celiac artery
complex arterial reconstruction was necessary. Due to
the small diameter of the donor hepatic artery a direct
anastomosis to the recipient supraceliac aorta was not
feasible so an allogenic iliac artery conduit was required.
The interposition graft was obtained from a heart-beat-
ing donor of a previous OLT and stored in histidine-
tryptophane-ketoglutarate solution at +4°C for 10 days.
Anastomosis of the bile duct was performed by duct-to-
duct anastomosis to the donor right hepatic duct
remnant.
At the time of transplantation the patient received
induction immunosuppression consisting of 500 mg
methylprednisolone and 20 mg basiliximab, the latter
was repeated on the 4th post-operative day (POD).
Immunosuppression was maintained with oral mycophe-
nolat mofetil from the first POD at 2 × 1 g daily and
oral prednisolone with an initial daily dose of 75 mg.
The latter was tapered by 5 mg every two days. On the
5th POD oral tacrolimus was added to the immunosup-
pressive regimen starting with 0.5 mg on the first day
and increasing daily dose by 1 to 2 mg to achieve trough
plasma level of 4-10 μg per liter. After surgery the reci-
pient received continuous intravenous infusion of 5000
units of unfractioned heparin per day for anticoagula-
tion. For prevention of (re-)infection the patient also
received 103 units of hepatitis B immunglobuline at
reperfusion and intravenous infusion of piperacillin/
tazobactam at surgery until the 3rd POD but no antimy-
cotics or prophylactic CMV therapy (both donor and
recipient had experienced CMV infection).
In the postoperative course serum transaminases
peaked on the first and 4th POD but then decreased
continuously as prothrombin time increased (coagula-
tion factors were not substituted). Albeit a gradual
increase in total bilirubin plasma levels only a mild graft
dysfunction was suspected because bile flow over the
T-drain increased. Daily doppler sonography of hepatic
vessels showed unaltered graft perfusion. Overall the
patient had an uncomplicated postoperative without
signs for infection or organ dysfunction. The clinical
course and laboratory findings did show mild a graft
dysfunction but neither rejection nor acute graft failure
were indicated.
On the 9th POD the patient suffered from acute para-
noid psychosis, being alert but agitated and physically
aggressive. He was mistrustful and afraid of being
harmed by people around him. The patient became
unmanageable and had to be sedated with an intramus-
cular injection of 5 mg haloperidol and an intravenous
injection of 20 mg diazepam. Due to this unusual pre-
sentation of postoperative delirium a diagnostic workup
was initiated. Patent hepatic artery could not be shown
in doppler sonography and subsequent angiography.
Explorative laparotomy on the same day revealed a com-
plete thrombosis of the donor hepatic artery and gross
ischemic infarction in all liver segments. Because pro-
gression of infarction and subsequent graft loss was to
be expected the patient was placed on the transplant
waiting list for re-OLT.
An acceptable organ was offered from an 18-year-old
heart-beating donor on the following day and the
patient underwent re-OLT 10 days after the LDLT. The
hepatic artery of the new graft was reanastomosed to
the old conduit. The immunosuppressive regimen was
reinitiated as described above including tacrolimus (see
Figure 1). Emergence from anaesthesia was uneventful
and the psychiatric symptoms did not recur in the post-
operative course. Furthermore a clinically suspected epi-
sode of acute rejection indicated by rising transaminases
was treated with a course of methylprednisolone (see
Figure 1). Daily doppler sonography of hepatic vessels
showed an unaltered graft perfusion. Examination of the
explant revealed thrombotic occlusion of the hepatic
artery with anaemic infarction of all liver segments.
Discussion
Here we describe a case of HAT after LDLT preceded
not by signs of an liver failure but by acute paranoid
psychosis. At transplantation the patient required a
complex arterial reconstruction with an interposition
graft which is a known risk factor for HAT [2,8].
Whether supraceliac or infrarenal placement of the
interposition graft is beneficial remains equivocal [1,9].
LDLT itself has also been implied to be a risk factor for
HAT, but Hatano et al could show increased incidence
of HAT only in ABO-incompatible grafts [5]. In the
described patient we observed a mild graft dysfunction
indicated by increasing bilirubin in the first week after
LDLT but accompanied by decreasing transaminases
Table 1 Characteristics of donor and recipient.
Donor Recipient
Age 43 yr. 42 yr.
Body weight 60 kg 73 kg 1.22*
BMI† 21 24 1.17*
Blood group A Rh pos. A Rh pos.
CMV IgG‡ pos. pos.
HBs-Ag neg. pos.
Anti-HBc pos. pos.
Anti-HBs > 1000 mlU/ml <10 mIU/ml
Anti-HCV neg. neg.
* Recipient/Donor ratio
† Body mass index
‡ Cytomegalo virus IgG status (IgM both neg.)
Goralczyk et al. BMC Surgery 2010, 10:7
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Page 2 of 5
Figure 1 Postoperative course of the patient. Postoperative course of the patient. Upper panel depicts aspartate transaminase (AST, solid line)
and alanine transaminase (ALT, dashed line) plasma levels in units per liter. In the middle panel total bilirubin (dashed line) and prothrombin
time (PT, solid line) in activity percentage is shown. The lower panel displays immunosuppression: methylprednisolone, black bars; prednisolone,
grey upper bars; basiliximab (Simulect), diamonds; tacrolimus trough levels, solid line and dots; tacrolimus dose, lower grey bars.
Goralczyk et al. BMC Surgery 2010, 10:7
http://www.biomedcentral.com/1471-2482/10/7
Page 3 of 5
and an increasing synthetic liver function. Daily doppler
sonography showed patent vessels until he suffered from
acute psychosis on the 9th postoperative day.
Psychiatric disorders are not uncommon in the post-
operative course of the liver transplant patient [10]. Like
other patients undergoing major surgery, transplant
patients may suffer from postoperative delirium. The
cause of delirium is multifactorial, including predispos-
ing factors (age, primary disease), medical/surgical fac-
tors (length of surgery, use of a cardiopulmonary bypass,
water-electrolyte imbalances, sepsis, etc), and postopera-
tive emotional stress, like prolonged sleep deprivation,
use of physical restraints, and pain [11,12]. In the
described patient postoperative delirium was unlikely
because after surgery delirium typically evolves immedi-
ately after emergence from general anaesthesia or, after
a lucid interval, in the first 72 hours [13].
Psychiatric disorders may also be drug induced.
Immunosuppressive drugs like tacrolimus and corticos-
teroids are known causative agents of psychiatric reac-
tions [14-16]. Neurotoxic effects are dose dependent
and occur in the early phase after initiation, e.g. within
the first week [14,16]. In our patient induction of the
described psychiatric symptoms by immunosuppressants
was also unlikely because the psychosis occurred after
the first week and doses were low, i. e., 5 ng/ml tacroli-
mus on the 9th postoperative day (see also Figure 1).
After re-transplantation he received tacrolimus and pre-
dnisolone again without any sign of recurrence of the
psychiatric disorder.
Because of elevated bilirubin we also suspected
impaired graft function could cause acute psychosis in
our patient. In chronic liver failure manifestations of
encephalopathy are common and may reach from mild
obtundation with dementia and movement disorders to
deep coma [17]. In the early phase of acute liver failure
agitation, delusional ideas, and hyperkinesis are also
common until coma finally ensues [18]. Although typical
laboratory findings of acute liver failure are common,
only moderate alteration, as seen in our patient, is not
an exclusion criterion [19]. In our patient ammonia was
also not elevated but in patients with more advanced
hepatocellular dysfunction the level of ammonia is only
poorly correlated with the severity of hepatic encephalo-
pathy [17]. Besides the accumulation of unmetabolized
ammonia other mechanisms have been implied as
causes of encephalopathy such as imbalance of neuro-
transmitters, endogenous benzodiazepine ligands, or ele-
vation of circulating tumor necrosis factor (TNF)
[19,20], some of them also involved in the pathogenesis
of sepsis-associated delirium [12].
Besides infection and sepsis surgical complications are
the most likely cause of graft dysfunction in the early
post-transplant period. Therefore we initiated further
diagnostic work-up. Abdominal sonography showed no
flow in the hepatic artery and subsequently HAT was
confirmed by angiography. During explorative laparot-
omy the liver was found to be with gross infarction and
we decided to evaluate the patient for re-transplantation.
Luckily we obtained a graft within 24 hours and after
re-transplantation psychosis resolved without sequelae.
Conclusion
We propose that in the described patient HAT is the
most likely cause of an acute liver failure although
laboratory findings indicated only mild graft dysfunction.
Acute liver failure was accompanied by hepatic encepha-
lopathy apparent as acute delusional psychosis.
This case highlights the need to remain suspicious
when psychiatric disorders occur in patients after liver
transplantation. The diagnostic procedures should not
be restricted to medical or neurological causes of psy-
chosis but should also focus vascular complications of
OLT.
Acknowledgements
Written informed consent was obtained from the patient for publication of
this case report and accompanying images. A copy of the written consent is
available for review by the Editor-in-Chief of this journal.
Author details
1Department of General and Visceral Surgery, University Medical Center
Göttingen, Göttingen, Germany. 2Department of Gastroenterology and
Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
Authors’ contributions
ADG and TL collected and analyzed the data and wrote the article. GR, HB
and AO contributed substantially to the process of analyzing the data and
writing the paper. All authors read and approved the final manuscript
Competing interests
The authors declare that they have no competing interests.
Received: 29 July 2009
Accepted: 22 February 2010 Published: 22 February 2010
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Cite this article as: Goralczyk et al.: Acute paranoid psychosis as sole
clinical presentation of hepatic artery thrombosis after living donor liver
transplantation. BMC Surgery 2010 10:7.
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Abstract Background Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications. Case presentation Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae. Conclusion This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.</p

Obed Aiman

Ramadori Giuliano

Meier Volker

Goralczyk Armin D

Lorf Thomas

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Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

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