| Revised: 22 October 2019 | Accepted: 9 December 2019

DOI: 10.1111/petr.13646  

CASE REPORT

Pediatric liver transplant following near catastrophic head
bleed: Lessons learned
Alex G. Cuenca1,2
| Stephen Hardy3 | Uzma Shah3 | David Lawlor4 | Zehra Ordulu5 |
Desiree Sierra Velez3 | Katherine Olshan3 | William Butler6 | Heidi Yeh1
1
Surgery/Abdominal Transplant,
Massachusetts General Hospital, Boston,
MA, USA
2

Abstract
Evaluation for liver transplant candidacy is a multidisciplinary effort that involves all

Pediatric Transplant Center, Boston
Children's Hospital, Boston, MA, USA

aspects of clinical care including social work, nutrition, and a multitude of medical

3
Pediatrics/Gastroenterology,
Massachusetts General Hospital, Boston,
MA, USA

decision to list a patient. Herein, we report a successful liver transplant and recov-

4

Surgery/Pediatric Surgery, Massachusetts
General Hospital, Boston, MA, USA
5

Pathology, Massachusetts General
Hospital, Boston, MA, USA
6

Neurosurgery, Massachusetts General
Hospital, Boston, MA, USA
Correspondence
Heidi Yeh, Surgery/Abdominal Transplant,
Massachusetts General Hospital, Boston,
MA, USA.
Email: [email-masked]

specialties. The prognosis of a pretransplant clinical condition is integrated into the
ery of a 3-month-old male following a large right hemispheric subdural hematoma
related to acute coagulopathy secondary to undiagnosed end-stage liver disease. On
presentation with jaundice, lethargy, and unequal pupils, a CT scan was obtained
which demonstrated a large right subdural hematoma with herniation. Once his coagulopathy was corrected, he went for decompressive craniectomy. He survived with
medically controlled seizures and improving L-sided neglect and extremity weakness.
Six weeks later, given his continued neurologic recovery and worsening liver function, the decision was made to list him for liver transplantation. One month later, he
underwent orthotopic liver transplant. His post-operative hospital course was complicated by DVTs and heparin-induced thrombocytopenia, but no neurologic decline,
and he was eventually discharged from the hospital on post-op day 26. Three years
later, he has a well-functioning allograft and no clinically evident neurologic deficits.
The prognosis following pediatric neurologic trauma remains somewhat unclear as
recovery and neurologic examinations can be influenced by numerous extrinsic factors. This is one of the first reports of near full neurologic recovery of a pediatric liver
transplant recipient following a large subdural hematoma with herniation.
KEYWORDS

intracranial haemorrhage, liver transplant, neurologic deficit

1 | I NTRO D U C TI O N

to ESLD. The etiology of liver failure during the neonatal period and
early infancy in this patient population includes metabolic disorders

Despite advances in our understanding of congenital diseases that

(tyrosinemia etc), biliary atresia, GALD, infection, and hypoxia-isch-

lead to liver failure in the pediatric population, there are still a signif-

emia-related hepatopathy.1,2 The most common presentation is

icant number of infants that present with late complications related

jaundice and hypoglycemia followed by renal failure, bleeding, and

Abbreviations: AASLD, American association for the study of liver diseases; AFP, alpha fetoprotein; BA, biliary atresia; DVT, deep venous thrombosis; ER, emergency room; ESLD,
end-stage liver disease; GALD, gestational alloimmune liver disease; HD, hospital day; ICA, internal carotid artery; ICH, intracerebral hemorrhage; INR, international normalized ratio;
MCA, middle cerebral artery; PCA, posterior cerebral artery; POD, post-op day; PRES, posterior reversible encephalopathy syndrome.

Pediatric Transplantation. 2020;00:e13646.
https://doi.org/10.1111/petr.13646

wileyonlinelibrary.com/journal/petr

© 2020 Wiley Periodicals, Inc.

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encephalopathy. 2,3 As might be expected, when these patients pres-

activity on EEG and required the addition of phenytoin for control.

ent, they are extremely ill and may be beyond the window to tolerate

The patient was extubated on POD 5 from decompressive craniec-

a liver transplant.

tomy and by POD 11 was able to take formula by enteric tube and

Regardless, most if not all patients will have a liver transplant

some by mouth but was neurologically asymmetric from a motor

evaluation initiated to determine candidacy for liver transplant.

standpoint (right side stronger than left). Once the patient was sta-

Per the most recent AASLD guidelines, absolute contraindications

ble from a hemodynamic, neurologic, and hematologic standpoint,

to pediatric liver transplant are currently extrahepatic malignancy,

decision was made to perform a cranioplasty. The patient ultimately

metastatic hepatocellular carcinoma or hepatoblastoma (beyond pul-

developed hydrocephalus and extra-axial fluid collections that ne-

monary metastasis), uncontrolled systemic infection, Niemann-Pick

cessitated ventriculopleural shunt placement. The patient tolerated

C disorder, severe multisystem mitochondrial disease, and severe

these procedures well.

portopulmonary hypertension not responsive to medical therapy.4

With regard to his liver failure, on admission, the patient was

Though severe neurologic damage has also been suggested as an

jaundiced with a total/direct bilirubin of 9.1/6.0 (mg/dL), petechiae,

absolute or relative contraindication to liver transplantation, a thor-

unrecordable INR, and an AFP of 14 000 (ng/mL). In addition, trans-

ough discussion with the institution's multidisciplinary committee

aminases were mildly elevated in the 200s (U/L). The patient also

will take each of these cases and other possible contraindication to

had notable hepatosplenomegaly. While the patient was being stabi-

liver transplant into consideration on a case by case basis.5 Focus

lized from a neurologic and hematologic standpoint, hepatology and

and attention is paid to those patients that are clinically improving

genetics were consulted. Metabolic, infectious, and toxic etiologies

or those that have the capacity for reversal of their symptomology

of liver failure were investigated and included cardiac echocardiog-

associated with liver failure.

raphy and CT imaging, as well as urine and serum testing for meta-

Herein, we present a 3-month-old patient that presented with

bolic hepatopathies and disorders of glycogen storage. In addition to

severe jaundice, coagulopathy, and intracranial hemorrhage. At the

this, whole exome sequencing was done as well. Unfortunately, all

time of liver transplant evaluation and listing, the patient had not

testing was found to be negative or non-diagnostic. A liver biopsy

fully recovered from a neurologic perspective. Although the risk was

was also performed which demonstrated severe liver failure, includ-

high for additional complications related to coagulopathy or neuro-

ing cholestasis, giant cells, ductular reaction with proliferation, and

logic insult, the decision was made to proceed with transplant.

fibrous septae. As the biopsy was not clearly conclusive for biliary
atresia or other etiologies of liver failure in an infant, he was treated

2 | CASE

for tyrosinemia preemptively and was therefore switched to tyrosine free formula and underwent nitisinone treatment as the risk of
treating him as having the presumptive diagnosis of tyrosinemia out-

The patient was a 3-month-old male with a history of neonatal jaun-

weighed the risk of not treating him as such.

dice, 2-month history of “bruising,” and increased vomiting over

Unfortunately, his liver function tests continued to deteriorate

the last 24 hours who presented to an outside hospital ER with in-

and a liver transplant evaluation was initiated at 4 months of age.

creased jaundice. Pt was discharged from the outside hospital ER

This multidisciplinary team included social work, nutrition, hematol-

but returned to our ER with right-sided ptosis, increased non-bloody,

ogy, physical and occupational therapy, hepatology, transplant sur-

non-bilious vomiting, and lethargy. On examination, the patient had

gery, and importantly, neurology and neurosurgery. On evaluation

asymmetric pupils (R 7-9 mm and L 3-4 mm), decorticate postur-

by team, the patient had recovered symmetric motor strength but

ing, and a tense fontanel. The patient was intubated and taken for

still had some evidence of left-sided neglect, neck muscle discoordi-

emergent CT scan. In addition, mannitol and hypertonic saline were

nation/weakness, and truncal hypotonia. While not fully recovered,

administered. CT scan revealed large right-sided subdural hematoma

the group felt his neurologic prognosis was quite good and was en-

with midline shift and uncal herniation (Figure 1). Neurosurgery was

couraged by his continued neurologic recovery from his initial insult.

emergently consulted but the patient was not taken to OR immedi-

Importantly, the group also felt strongly that he could and would

ately due to coagulopathy (INR was unrecordable). After correcting

continue to recover with a liver transplant but would not survive

coagulopathy with fresh frozen plasma and IV vitamin K, the patient

without one.

was taken to the OR for a right craniectomy with hematoma evacua-

A suitable deceased donor liver became available approximately

tion on HD 2. Post-operatively, the patient required continued fresh

one month later and the patient, now 5 months old, underwent an

frozen plasma for correction of severe coagulopathy suggestive that

orthotopic liver transplant with Roux-en-Y hepaticojejunostomy in

the etiology of the coagulopathy was not a nutritional or absorption

the absence of recipient common or hepatic bile duct. The patient

deficiency of vitamin K. Neurologic examination was limited due to

did well post-operatively with excellent hepatic allograft function.

sedation but spontaneous bilateral eye opening as well as brain stem

During his post-operative course, the patient did develop DVTs of

reflexes (gag and corneal) were observed. Repeat head imaging re-

his IVC and right iliac vein and so a hypercoagulable work-up was

vealed no additional bleeding but evidence of ischemia to the right

initiated. The patient was found to be heparin-PF4 antibody posi-

ICA, MCA, and PCA territories. Despite seizure prophylaxis insti-

tive, and therefore, DVTs were thought to be attributable to hepa-

tuted at the time of presentation, the patient also had epileptiform

rin-induced thrombocytopenia. Our hematology colleagues agreed.

CUENCA et al.

F I G U R E 1 Axial (A) and coronal (B)
computed tomography sections of the
patient's head on presentation to our ER

F I G U R E 2 Gross and microscopic
evidence for common bile duct
atresia. A, Cirrhotic liver with green
discoloration and bile plugs. B, Atretic
common bile duct. C, Xanthomatous
transformation of hepatocytes with
surrounding cholangiolar proliferation. D,
Prominent bile plug. E, Trichrome staining
highlighting the fibrosis (blue) in cirrhotic
transformation

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CUENCA et al.

Pt was maintained on fondaparinux for 6 months without bleeding

hemorrhage due to BA.9 Akiyama and colleagues found that the

complication or issue. The patient was discharged from the hospital

incidence of ICH in BA in their center was approximately 8% (15

on POD 26 from liver transplant playful, interactive, without focal

of 194).9 Of these, three patients developed hemiparesis that re-

deficits, and tolerating PO feeds. Final pathology from the native

solved completely. Most patients survived following either a por-

liver demonstrated marked cholangiolar proliferation with associ-

toenterostomy alone or a portoenterostomy following by transplant

ated bile plugs, xanthomatous transformation of hepatocytes, and a

(11 of 15), and less than a third (2 of 15) had long-term neurologic

trichrome stain that showed dense fibrous periductular septae and

sequelae, which included mental retardation (2 cases) and epilepsy

other features of cirrhotic transformation, all consistent with extra

(1 case).9

hepatic biliary atresia (Figure 2).

Neurologic complications are also not uncommon post-opera-

The patient presented to clinic recently, 3 years following trans-

tively following a liver transplant. One single-center study by Gungor

plant, meeting all developmental milestones and doing well aside

et al found that 24% of their pediatric patients developed neurologic

from the occasional upper respiratory infection. For immunosup-

symptoms following liver transplant.6 This included encephalopathy

pression, the patient is maintained on tacrolimus only and has had

and seizures most commonly to PRES and hemiparesis/paralysis in

normal liver function laboratories.

others.6 The etiology for these neurologic changes was multifactorial but thought to be related to mostly immunosuppression, hypoxic/ischemic brain injury, and metabolic derangements. Clearly,

3 | D I S CU S S I O N

our patient was at extremely high risk for developing post-operative
seizures secondary to his history of prior intracranial hemorrhage

The incidence of infant-related (within the first 120 days of life)

and seizure activity. In spite of this, our patient did well following the

acute liver failure is difficult to discern as there are only few contem-

liver transplant and continued to improve neurologically.

porary cohort studies available and by and large they are from single
2

To the best of our knowledge, this case represents the first re-

centers. As biliary atresia is the most common reason for pediatric

ported near full neurologic recovery of a pediatric liver transplant

transplant, progressive and relatively rapid liver failure from biliary

recipient following a large acute subdural hematoma with herniation.

atresia can occur and usually presents in the form of coagulopathy.

Though this neurologic event would likely make him ineligible for

The coagulopathy can lead to intracranial hemorrhage and subse-

transplant at most centers, we were encouraged by his pretransplant

quent irreversible neurologic sequelae. Fortunately, in our patient,

neurologic improvement and knew that he would not survive with-

these changes were reversible.

out a liver transplant. Therefore, while this case is unique and cannot

The decision of whether or not to proceed with an organ trans-

be generalized to all similar clinical scenarios, it has broadened our

plant in a child within the first year of life is not straightforward and

discussion as to whether or not pediatric patients with acute neuro-

requires the discussion of a multidisciplinary team. As the number of

logic events such as the one described above are eligible for organ

potential recipients still far outweighs the numbers of donors, most

transplantation. It also highlights the importance of multidisciplinary

centers agree that the allocation of livers in this population should

cooperation in the successful management of complex transplant

be relegated to those that have failed conventional medical ther-

candidates. Further, it would be useful to review large international

apy and/or are at serious risk of death within the first year of life. In

biliary atresia registries to assess outcomes in patients with pre-LT

addition, even though liver transplant outcomes have dramatically

neurological morbidity, for a better representation of outcomes.

improved in this age group due to refinements in technique, as well
as more experience with split or living donor liver surgery, technical
complications are still thought to be greatest in this age group.

6,7

C O N FL I C T S O F I N T E R E S T
The authors of this manuscript have no conflicts of interest.

Despite these hurdles, outcomes following orthotopic liver
transplant in the infant population are quite good and continue to

AU T H O R S ' C O N T R I B U T I O N S

improve. Overall 1-, 5-, and 10-year survival rates for pediatric pa-

AG. C and HY: Conceived the manuscript, edited, analyzed and in-

tients undergoing liver transplant are approximately 90%, 80%, and

terpreted the data; SH, WB, and US: Conceived the manuscript; US:

70%, respectively, compared to 75%, 65%, and 60% 10 years ago.8

Conceived and edited the manuscript; ZO: Reviewed and edited

In fact, long-term outcomes have been so good that some focus has

the figure and manuscript; DS. V and KO Reviewed and edited the

now been shifted from survival of the pediatric liver transplant pa-

manuscript.

tient to improvement in quality of life metrics and minimizing the
developmental delays associated with liver transplant.4
Given the excellent survival following liver transplant, his con-

ORCID
Alex G. Cuenca

https://orcid.org/0000-0002-6219-7035

tinued neurologic improvement, and the persistent coagulopathy
despite product administration, we decided to proceed with a liver

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How to cite this article: Cuenca AG, Hardy S, Shah U, et al.
Pediatric liver transplant following near catastrophic head
bleed: Lessons learned. Pediatr Transplant. 2020;00:e13646.
https​://doi.org/10.1111/petr.13646​