| |

Received: 30 May 2018    Revised: 7 November 2018    Accepted: 28 January 2019

DOI: 10.1111/petr.13396

ORIGINAL ARTICLE

Utility of neonatal donors in pediatric liver transplantation:

A single‐center experience

Wei Gao1,2 | Zhuolun Song1,2  | Nan Ma1,2 | Chong Dong1,2 | Chao Sun1,2 |

Xingchu Meng1,2 | Wei Zhang1,2 | Kai Wang1,2  | Bin Wu1,2 | Shanni Li1,2 |
Hong Qin1,2 | Chao Han1,2 | Haohao Li1,2 | Zhongyang Shen1,2

1
Liver Transplantation Department, Tianjin
First Center Hospital, Tianjin, China
2
Tianjin Key Laboratory for Organ
Transplantation, Tianjin, China
Correspondence
Zhongyang Shen, Organ Transplantation
Center, Tianjin First Center Hospital, Tianjin,
China.
Email: zhyshentjfch@sina.com
Funding information
This study was funded by Tianjin Clinical
Research Center for Organ Transplantation
Project (15ZXLCSY00070) and Key Project
of Tianj​in Healt​h and Famil​y Plann​ing Commi​
ssion​ (16KG107).
Abstract
Background: The lack of age‐ and size‐matched organs result in higher waiting list
mortality in pediatric recipients than adults. Organs from deceased newborns and
infants are a valuable source to increase donor pool in pediatric liver transplanta‐
tion. However, the feasibility and safety of using neonatal donors have not been well
evaluated.
Methods: From 2014 to 2016, 48 deceased donor pediatric liver transplantations
with donor age younger than 1 year old in our center were enrolled in this study. The
recipients were divided into three groups based on the donor age (<1 month, 1 month
≤ to <3 months, and 3 months ≤ to <1 year). Recipient's characteristics, perioperative
data, and postoperative complications were compared.
Results: Two‐year patient survival rates were 87.5%, 94.4%, and 95.5%, and 2‐year
graft survival rates were 75%, 94.4%, and 95.5%, respectively, without significant
difference. The liver grafts from donors younger than 3 months were more advanta‐
geous in terms of acute rejection and virus infection, while the young grafts were
related to slight higher incidence of hepatic artery thrombosis and SFSS. Those com‐
plications could be effectively prevented or treated by our perioperative care strate‐
gies. In addition, eight recipients who received neonatal livers achieved comparable
outcomes with recipients with older livers.
Conclusion: Our data revealed that the application of liver grafts from donors younger
than 1 year old could achieve excellent outcome. In particular, neonatal donors could
be safely used in well‐selected patients.

KEYWORDS
acute rejection, hepatic artery thrombosis, neonatal donor, pediatric liver transplantation,
SFSS

Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CLTR, china liver transplant registry; CMV, cytomegalovirus; DBD, donation after brain
death; DBIL, direct bilirubin; DCD, donation after cardiac death; EB virus, Epstein‐Barr virus; GRWR, graft‐to‐recipient weight ratio; ICU, intensive care unit; INR, international normalized
ratio; LDLT, living donor liver transplantation; MMF, mycophenolate mofetil; PELD, pediatric end‐stage liver disease; PTCD, percutaneous transhepatic cholangial drainage; SFSS, small‐
for‐size syndrome; TBIL, total bilirubin; UNOS, united network for organ sharing.

Pediatric Transplantation. 2019;00:e13396. wileyonlinelibrary.com/journal/petr © 2019 Wiley Periodicals, Inc.  |  1 of 9

https://doi.org/10.1111/petr.13396
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2 of 9       GAO et al.

1 |  I NTRO D U C TI O N
With the progress of surgical skills, immunosuppressive therapy, and
perioperative patient care, pediatric liver transplantation has be‐
come a well‐established strategy in treating end‐stage liver disease
and acute liver failure in children.1,2 Unlike adult liver transplantation
in which the recurrence of primary disease is a major concern after
operation,3 liver transplantation in children offers an ideal treatment
to completely eliminate the pathogenic factor and a better long‐term
4
outcome can be expected. Nevertheless, the scarce availability of
donor liver is still a main reason that hinders the expansion of liver
transplantation, and this problem is particularly obvious in small chil‐
dren because of a lack of suitable age‐ and size‐matched graft. This
situation has led to four times higher waiting list mortality rate in
children recipients younger than 6 years compared with those aged
between 11 and 17 years.5,6
Nowadays, the main graft type for pediatric liver transplan‐
tation is split liver grafts from adult deceased and living donors,
and less attention has been given to the utility of donor livers from
deceased young children, 8,9
especially to grafts obtained from
newborns or infants. The data from the UNOS have shown that
pediatric donors are more favorable for pediatric recipients than
adult recipients; therefore, pediatric recipients should be consid‐
ered first when allocating pediatric liver grafts. 10
In fact, the liver
grafts from young children could not only provide size‐appropriate
5
grafts but also increase the availability of donor livers. There are
only few reports concerning the usage of young pediatric organs
in pediatric liver transplantation. 2,9 In this study, we aim to analyze
the outcome of pediatric recipients who obtained livers from do‐
nors younger than 1 year, with a special focus on the feasibility of
using neonatal donor livers.
2 | PATI E NT S A N D M E TH O DS
2.1 | Donor and recipient data
Between 2014 and 2016, a total number of 421 pediatric liver
transplantations were performed in Tianjin First Center Hospital.
The overall 2‐year graft and recipient survival rates were 95.7%
and 96.4%, and no difference was observed among living donor,
deceased donor, and split liver transplantations. 104 out of the
recipients received deceased donor livers. Fifty‐five of the de‐
ceased donors were older than 1  year and were excluded from
our study; one recipient received re‐transplantation; the first
donor age was less than 1 month; the second donor age was
7 4 months; and his second transplantation was excluded from the
study due to statistical reasons of repeated grouping. The re‐
maining 48 transplantations were divided into three groups ac‐
cording to the donor age: group 1: donor age < 1 month (n = 8);
group 2:1  month  ≤  donor age  <  3  months (n  =  18); and group
3:3 months ≤ donor age < 1 year (n = 22). This study was approved
by the institutional review board of Tianjin First Center Hospital
(approval number: 2016N054KY).
The donor type in this study was mostly DBD, with a small
portion of DCD donors. Criteria and practical guidance for de‐
termination of brain death in children formulated by Brain Injury

TA B L E 1   Donor characteristics
Group 1 Group 2 Group 3
  n = 8 n = 18 n = 22

Age (mo) 0.6 ± 0.3 1.6 ± 0.5 6.8 ± 2.7a,b

Height (cm) 51.3 ± 6.6 58.3 ± 6.3 67.2 ± 5.7a
2c 4c 3c
Weight (kg) 3.6 ± 0.5 4.1 ± 0.7 7.7 ± 3.0a
1c 2c
Gender (female/male) 3/5 9/8 11/11
1c
Donor type
DBD 7 15 19
DCD 1 3 3
Blood test
ALT (U/L) 37.0 (7.0, 52.0) 18.2 (12.3, 28.3) 28.3 (13.0, 40.4)
AST (U/L) 27.2 (16.5, 67.0) 22.9 (21.3, 44.1) 36.0 (25.0, 65.0)
TBIL (μmol/L) 8.5 (5.1, 48.0) 7.7 (3.5, 30.5) 7.2 (4.8, 14.0)
Graft weight (g) 135.8 ± 38.9 130.2 ± 16.9 228.9 ± 76.0a,b
GRWR (%) 2.4% ± 0.7% 2.0% ± 0.4% 3.5% ± 1.5%a,b
P < 0.05.
a
1 vs 3.
b
2 vs 3.
c
Missing data.
GAO et al. |
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Evaluation Quality Control Centre of National Health and Family

Planning Commission in China and guidelines for the determi‐
nation of brain death in children from American Academy of
Pediatrics Task Force on brain death in children were adopted
to define brain death in donors.11,12 Regarding DCD donation,
donor death was determined by invasive blood pressure as well
as cardiac ultrasound and was declared 2‐5 minutes after circu‐
lation cessation.13 The informed consents from donor families
were properly obtained, and the organ donation and allocation
were based on the regulations of CLTR. No organs from executed
prisoners were used. The donor and recipient's characteristics
were shown in Tables 1 and 2, respectively. Three groups were
compared in terms of primary diseases, preoperative status, op‐
erative process, postoperative complications, and graft/patient
survival.
2.3 | Pediatric whole liver transplantation
The donor livers were procured from donors younger than 1 year old.
Therefore, the appropriate size‐matched livers allow us to perform
piggy‐back orthotopic liver transplantation with whole livers to all the
pediatric recipients. The grafts implantation starts with the anastomo‐
sis of donor upper vena cava to the common orifice of two or three
hepatic veins. The donor and recipient portal veins were anastomosed
end‐to‐end with running suture. The reperfusion of the donor liver
was achieved after portal vein anastomoses were completed. Hepatic
artery reconstruction was performed according to the size of arter‐
ies under the surgical loop or microscope with interrupted suture. The
biliary reconstruction was performed at the final stage, and the Roux‐
en‐Y anastomosis (hepatojejunostomy) was done in the recipients with
biliary atresia using interrupted suture. All the operations were per‐
formed by the same group of highly proficient transplant surgeons.

2.2 | Procedure of organ procurement

A well‐trained surgical team was responsible for organ procurement,
and the same procurement method was followed in this study. The
donor livers were perfused with University of Wisconsin (UW) solu‐
tion through both portal vein and abdominal artery. Heparin (400
unit/kg) was given via the central venous catheter several minutes
before aortic cross‐clamp. The donor livers were preserved in the
UW solution during transportation.
2.4 | Postoperative management
All the recipients received intensive care in a specialized transplant
ICU in our center, and routine blood test and clinical examination
were performed daily in the first week after surgery to evaluate the
recovery of liver function. In order to monitor the patency of blood
flow, Doppler ultrasound was performed daily in the first postopera‐
tive week. Further measurement was applied if clinically indicated.

TA B L E 2   Recipient characteristics
Group 1 Group 2 Group 3
  n = 8 n = 18 n = 22

Age (mo) 6.5 (5.3, 8) 7.5 (5.8, 10) 6 (5, 7.5)

Height (cm) 62.8 ± 3.5 63.3 ± 5.8 64.0 ± 5.6
Weight (kg) 6.0 ± 1.2 6.5 ± 1.1 7.4 ± 3.1
a
Gender (female/male) 7/1 6/12 14/8
Diagnosis
Biliary atresia 8 (100%) 17 (94.4%) 21 (95.5%)
Genetic disease 0 1 (5.6%) 0
2nd liver transplantation 0 0 1 (4.6%)
Kasai procedure 3 (37.5%) 10 (55.6%) 9 (40.9%)
Preoperative status
Ascites 2 (25%) 2 (11.1%) 8 (36.7%)
Cholangitis 1 (12.5%) 1 (5.6%) 3 (13.6%)
Preoperative blood test
ALB (g/L) 35.0 ± 5.3 34.2 ± 5.6 33.7 ± 5.3
TBIL (μmol/L) 219.4 ± 62.0 291.5 ± 148.3 261.2 ± 109.6
DBIL (μmol/L) 120.6 ± 51.5 132.3 ± 69.5 140.9 ± 69.4
INR 1.2 (1.0, 1.9) 1.3 (1.0, 1.9) 1.3 (1.0, 1.5)
PELD score 28.17 ± 10.0 28.7 ± 10.5 27.8 ± 10.4
Child score 8.4 ± 1.3 8.2 ± 1.4 8.7 ± 1.7

P < 0.05.
a
1 vs 2.
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Basiliximab was given during the operation for immune induc‐
tion. Postoperatively, tacrolimus (FK 506) and steroids were used
as immunosuppressive agent. The plasma concentration of FK 506
was kept between 7 and 10  ng/mL in the first 3  months. 10  mg/
kg steroids was given in the time of operation; hereafter, steroids
were intravenously administrated in the following 5 days, and oral
administration starts from the 6th postoperative day. The applica‐
tion of steroids was withdrawn after 6 months of transplantation.
Steroid bolus therapy was given to recipients once acute rejection
occurred.
In order to prevent hepatic artery thrombosis, anti‐coagulative
treatment was routinely given to all the recipients when INR was
lower than 1.5. Low molecular weight heparin was given in the first
postoperative week, and warfarin was added in the 5th postoper‐
ative day. The value of INR should be maintained between 1.5 and
2.0. The anti‐coagulative therapy normally lasted 6  months with
possibly prolongation in recipients with vascular stenosis.
2.5 | Statistical analysis
The continuous data were firstly analyzed by Kolmogorov‐Smirnov
test and were described as mean/standard or median/range de‐
pending on the distribution. One‐way ANOVA was applied to ana‐
lyze normal distribution data, and in case of abnormal distribution,
Kruskal‐Wallis test was performed. Categorical variables were ex‐
pressed as number/percentage. Differences were calculated with
chi‐square test. The survival rate of graft and patient was evaluated
by Kaplan‐Meier survival curves and compared with Log Rank test.
The statistics were performed using the SPSS 23.0 software (IBM,
München, Germany). Statistical differences were considered signifi‐
cantly when P < 0.05.
3 |   R E S U LT S
3.1 | Donor characteristics
All the donors in this study were younger than 1 year old, and the
donor characteristics were shown in Table 1. The groups were clas‐
sified by donor age, and as expected, the age, height, body weight,
and graft weight in group 3 (3 months ≤ donor age < 1 year) were
significantly higher than group 1 (donor age < 1 month) and group
2 (1 month ≤ donor age < 3 months). The donor type was shown in
Table 1, the mean warm ischemic time for DCD donors was 3 min‐
utes, and no difference was observed among three groups.
3.2 | Recipient characteristics
According to the donor age, the recipients were divided into
three groups. Although the donor age, height, and body weight
were significantly higher in group 3 compared with groups 1
and 2, no significant difference was observed in terms of age,
height, and body weight of recipients among three groups. Due
to the availability of size‐matched organs, all the recipients
received whole liver transplantation, apart from the difference
of graft weight in group 3, and the GRWR in group 3 was also
significantly higher than the other two groups. Biliary atresia
is the major reason for liver transplantation in this study; only
one case in group 2 was diagnosed of Alagille syndrome, and
one case in group 3 underwent 2nd liver transplantation due
to graft failure. There was no difference in the distribution of
diagnoses among three groups. We measured the level of TBIL,
DBIL, ALP, and INR to represent the function of liver and the
severity of disease before the operation in order to evaluate
the state of illness, and we did not observe any significant dif‐
ference among three groups. In regard to PELD and Child‐Pugh
score which may influence the outcome of recipients, all three
groups were comparable.
3.3 | Intraoperative phase
There was no significant difference with regard to the cold ischemic
time and total operation time in all groups, and the blood loss was
also equal in three groups. Interestingly, the anhepatic phase in
group 2 was significantly shorter than group 1. This can be partially
explained by the complexity of surgery when using smaller liver graft
(Table 3).
3.4 | Early postoperative recovery
We consider the first postoperative week as the critical phase; all
the children overcame and survived after surgery, and only one child
who received a liver from a 3‐day old donor died on the 7th day after
operation. There was no difference in the peak level of postopera‐
tive ALT, TBIL, blood ammonia, and lactic acid in all three groups. The
ICU and hospital stay were also comparable (Table 3).
3.5 | Postoperative complications
In our study, the children in group 1 showed insignificant higher rate
of hepatic artery thrombosis and portal vein stenosis compared with
groups 2 and 3. The percentage of hepatic artery thrombosis were
50.0%, 33.3%, and 26.1% in groups 1, 2, and 3, respectively, and
all of the cases were diagnosed by routine Doppler ultrasound in
the first postoperative week. In most of the recipients with hepatic
artery thrombosis, we reinforced the anti‐coagulative therapy, and
the blood flow was re‐established or the collateral circulation was
formed. One child in group 2 underwent surgical intervention to re‐
vise the hepatic artery, and one child died in group 1 after hepatic
artery blocking. No difference has been shown in terms of portal
vein stenosis and thrombosis in all groups.
SFSS was defined clinically if cholestasis, prolonged coagulopa‐
thy, portal hypertension, and ascites appeared,14 and it occurred in
two recipients in group 1 and 4 recipients in group 2. Four out of the
six recipients with SFSS developed hepatic artery thrombosis. None
of the recipients developed SFSS in group 3, and this may due to the
application of larger donors in group 3.
GAO et al. |
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TA B L E 3   Liver transplantation Operation

procedure
Total operation time (h) 9.4 ± 1.8 8.7 ± 1.7 8.2 ± 1.1
Cold ischemic time (h) 8.0 ± 2.9 6.9 ± 4.6 8.8 ± 2.5
a
Anhepatic phase (min) 76.8 ± 35.7 53.4 ± 11.1 57.1 ± 14.8
Blood loss (mL) 437.5 ± 176.8 508.3 ± 510.8 327.3 ± 196.8
ICU stay (d) 3.9 ± 1.2 5.3 ± 3.9 3.5 ± 1.4
Hospital stay (d) 34.3 ± 20.4 35.8 ± 21.8 42.5 ± 33.3
Postoperative blood test
Peak ALT (U/L) 262.5 (208, 365.3) 267.5 (215.3, 565.1) 483.5 (323.6,
1096.5)
Peak TBIL (μmol/L) 255.0 (194.3, 272.0) 367.5 (246.0, 461.0) 285.0 (181.3,
374.8)
Peak blood ammonia 121.0 (112.0, 150.5) 90.0 (85.0,123.0) 87.5 (70.0,
(μmol/L) 3b 1b 116.8)
3b
Peak lactic acid (mmol/L) 4.1 (2.7, 6.1) 3.3 (2.4, 4.4) 2.4 (1.8, 4.5)
3b

P < 0.05.
a
1 vs 2.
b
Missing data.

F I G U R E 1   Postoperative
complications in groups 1‐3 (A, P < 0.05
when 1 vs 2; B, P < 0.05 when 1 vs 3; C,
P < 0.05 when 2 vs 3)

Biliary complications were comparable among three groups. For Two recipients suffered from bilioenteric anastomosis leakage, and
the recipients who suffered from stenosis of bilioenteric anastomo‐ in both of them, the leakage occurred a few days after the hepatic
sis, we used PTCD plus balloon dilation as our standard treatment. artery thrombosis.
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6 of 9       GAO et al.
F I G U R E 2   A, Survival analysis of recipient depending on donor age. The figure shows the Kaplan‐Meier curves of recipient survival in
groups 1‐3. B, Survival analysis of graft depending on donor age. The figure shows the Kaplan‐Meier curves of graft survival in groups 1‐3
Despite the high percentage of vascular complications, the recip‐
ients in groups 1 and 2 showed superior outcomes in terms of acute
rejection and infection. Acute rejection occurred in only 1 child in
group 1, and none of the recipients developed acute rejection in
group 2; group 3 showed significantly higher chance of acute rejec‐
tion compared with the other two groups combined. As for postop‐
erative infection, no recipient in group 1 had pulmonary infection;
likewise, EB virus infection in groups 1 and 2 was less than group
3, while group 2 had significantly lower rate of CMV infection com‐
pared with group 3 (Figure 1).
3.6 | Graft and recipient survival
The median follow‐up was 28.5, 30, and 30 months in groups 1, 2,
and 3, respectively. In group 1‐3, the 2‐year recipient survival rates
were 87.5%, 94.4%, and 95.5% (Figure 2A). Statistical analysis re‐
vealed no significant difference with regard to the graft survival rate
in all groups.
The survival rate of graft was 75%, 94.4%, and 95.5% after
2  years in groups 1‐3 (Figure 2B). No significant difference was
observed among all groups. One recipient in group 1 received re‐
transplantation due to hepatic artery thrombosis and leakage of bil‐
ioenteric anastomosis.
4 |  D I S CU S S I O N
To our knowledge, there are only few publications concerning the
application of deceased donors from young children in pediatric liver
transplantation and the results are still controversial. 2,9,15 Based
on the long‐term accumulated experience in our transplantation
center, together with organ allocation system of CLTR, we routinely
use donor livers from young children, including neonatal or infant
donors, to strictly selected recipients. In this study, we report that
donor livers younger than 1 year old could be safely used in children
recipients; in particular, the application of neonatal donors could
achieve excellent recipient outcome, and it enables this type of do‐
nors as an ideal option to expand the availability of donor livers in
pediatric liver transplantation.
The same as in adult patients, liver transplantation is also the
only curative method for end‐stage liver diseases in children.
Although LDLT has provided life‐saving organs and the technical
variant grafts such as split grafts have been associated with ideal
results,16,17 the scarce availability of size‐matched organs for young
children has still resulted in the highest morbidity and mortality rate
of children patients on the waiting list, almost twice as many as adult
recipients.18-22 New born babies have the highest mortality rate;
therefore, donors at this age could offer substantial source of size‐
matched organs for pediatric liver transplantation. 23 Nevertheless,
so far, there was only one publication reporting the application of
neonatal livers, and many centers still dare not to use this type of
organs due to the technical difficulties and the concern of organ
immaturation. 2,9
In the present study, we noted that the 2‐year survival rate in
patient and graft was 87.5% and 75% in group 1 which has no signif‐
icant difference compared with groups 2 and 3. The survival rate of
both patient and graft using neonatal donors in our study was better
than the data from Yokoyama.9 This may result from the advanced
GAO et al.
progress of surgical skills and perioperative management after two
decades. Two graft loss happened in group 1, both occurred after
hepatic artery thrombosis, one of those died 7 days after transplan‐
tation, and the other one underwent re‐transplantation. Compared
with adult organs, the pediatric organs are not only smaller in size
but also in the diameter of vessels, this feature increases the difficul‐
ties of surgery and also the chance of vascular complications, 24 and
vascular complication is one of the main cause of graft failure after
pediatric liver transplantation. This type of complication is more
25
likely to occur in recipients with small liver grafts. Previous studies
have reported that young donor age was associated with hepatic ar‐
tery thrombosis. 26 Another one claimed that hepatic artery diameter
less than 3  mm was a risk factor for hepatic artery thrombosis. 27
Due to the young donor age, majority of the donor hepatic arteries
in our study were less than 3 mm, especially in group 1. As expected,
the occurrence rate of hepatic artery thrombosis in group 1 was
higher while group 3 had the lowest rate of hepatic artery thrombo‐
sis although the difference was insignificant among all groups. Once
hepatic artery thrombosis occurred, we used to re‐anastomose the
hepatic artery if the arterial flow is not detectable by ultrasound.
However, this treatment only led to short‐term revascularization,
and hepatic artery thrombosis happens again in most cases after a
few days. Thus, we currently apply conservative therapy by inten‐
sifying anti‐coagulation treatment with low molecular weight hep‐
arin, warfarin, and alprostadil immediately to children when HAT is
confirmed. This treatment is associated with better revascularization
and the formation of collateral circulation. The blood supply to the
biliary system is mainly coming from the hepatic artery, 28 and the
thrombosis of hepatic artery may lead to the postoperative biliary
29
complications. This theory was supported by our data that one
patient in group 1 and one in group 2 developed bile leakage a few
days after the formation of hepatic artery thrombosis. Apart from
that, there was no significant difference in three groups with regard
to biliary complication.
The overall standard liver weight in adults is approximately
2%‐3% depending on the age and race.30 In children, however, the
liver weight is age‐dependent, and the maximal liver weight can
31
reach 5% of the body weight in some cases. Therefore, what is
the safe range of GRWR in pediatric liver transplantation still needs
to be further assessed. Previous studies have suggested that grafts
with GRWR <1% could be regarded as small‐for‐size grafts,32,33
34,35
while GRWR >4% were classified as large‐size grafts. We ad‐
opted this experience‐based classification as our standard to eval‐
uate the influence of GRWR on the recipient outcome. The mean
GRWR in groups 1‐3 was 2.35%, 2.03%, and 3.49%, and all met the
criteria of size‐matched organs. SFSS is rarely discussed in adult de‐
ceased donor liver transplantation; nevertheless, this issue appears
more noteworthy in pediatric deceased donor liver transplantation
due to the unbalanced growth between donors and recipients. SFSS
happened in six children in our study, two in group 1 and four in
group 2, and the GRWR in those children was all between 1.5% and
1.8%, lower than the mean GRWR of the two groups. Four out of
those six recipients developed hepatic artery thrombosis. Of note,
|
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only one recipient in this study had a GRWR less than 1%, and this
recipient did not develop SFSS, but hepatic artery thrombosis oc‐
curred. These data were in consistent with the previous reports that
small liver graft was associated with hepatic artery complications.36
None of the recipients in group 3 developed SFSS, and the incidence
rate was significant lower than groups 1 and 2. This can be explained
by the fact that group 3 had significantly higher donor age, weight,
and GRWR. Six children in group 3 received large‐size grafts (GRWR
>4%), these large grafts could fit well into the abdomen, and the re‐
cipients achieved equal outcome with other recipients who received
size‐matched organs. Thus, our data supported the previous report
that large‐for‐size transplantation in children did not influence the
postoperative outcomes.32
In spite of the fact that neonatal (group 1) and infant (group 2)
grafts seemed to have higher rate of SFSS, the recipients in these two
groups showed favorable outcome in acute rejection, and the recip‐
ients in group 3 exhibited significantly higher rate of acute rejection
compared with the combination of groups 1 and 2 in our study. It
has long been claimed that immune tolerance is more likely to be
induced in children due to the immatureness of immune system.36-38
The immunosuppressive protocol in our center for recipient younger
than 6 years old is the combination of tacrolimus and steroids, un‐
like adult recipients, MMF is not considered unless in recipients who
received ABO incompatible donors or had high risk of postoperative
immune rejection. In the present study, we showed that the donor
age younger than 3 months had lower rate of acute rejection; thus,
it can be speculated that not only the age of recipients but also the
age of donors may have impact on the postoperative acute rejec‐
tion. Interestingly, the recipients in group 1 and in particular group
2 showed superior results in terms of virus infection compared with
group 3. Rejection and infection are regarded as a pair of contradic‐
tory players in the field of organ transplantation, and the immuno‐
suppressive therapy is usually related to compromised anti‐infection
capability.39,40 It is worth noting that no recipients in group 2 had
acute rejection and virus infection. Whether donors at this age are
more advantageous in the interaction of rejection and infection still
needs to be investigated, and our study at least showed that donor
livers younger than 3  months old have decreased chance of acute
rejection and virus infection compared with older donors which are
considered to be more mature.
Another concern which limits the application of neonatal and
infant donors is the immatureness of organs. 2 It has been consid‐
ered that the immature organs may have negative impact on the
recovery of the transplanted organs as well as the recipient sur‐
vival rate.41 In our study, apart from the equal survival rate, we
have also demonstrated that the early graft recovery presented by
postoperative peak ALT, TBIL, blood ammonia, and lactic acid in
neonatal and infant donors was also comparable with donor livers
older than 3 months. The duration of liver maturation and devel‐
opment varies among different individuals,42 and our study has
shown that the livers from extreme young donors, although are
considered immature, are sufficient to support the daily needs for
the recipients.
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8 of 9       GAO et al.
In spite of the encouraging results, our study has some limita‐
tions, this is a single‐center study, and the utility of neonatal donors
is a newly accepted measure in our center with the progress of sur‐
gery and patient management; therefore, we still do not have a large
registry regarding this topic. For the next step, more patients from
a large registry in our country will be analyzed and further studies
should be followed to evaluate the long‐term outcomes.
All in all, our data convincingly showed that neonatal donor liv‐
ers could safely be applied to well‐selected pediatric recipients, and
comparable postoperative outcome was observed compared with
recipients who received donors from older children. This type of
organs offers a precious source of size‐matched organs in pediat‐
ric liver transplantation. Although we saw an increasing tendency of
hepatic artery thrombosis with the decrease of donor age, our treat‐
ment protocol was able to restore hepatic artery blood flow in most
cases. In addition, neonatal and infants donors exhibited advantage
in the aspect of acute rejection and virus infection. Further clinical
investigation with a large registry and basic research are needed to
investigate the clinical potential and superiority of the utility of ex‐
treme young donors.
AC K N OW L E D G M E N T S
We would like to thank Ms. Yu Cao for her excellent support in sta‐
tistical analysis.
C O N FL I C T O F I N T E R E S T
The authors of this manuscript have no conflicts of interest to
disclose.
AU T H O R S ’ C O N T R I B U T I O N S
Wei Gao and Zhongyang Shen: Designed study; Zhuolun Song,
Nan Ma, Chong Dong, Chao Sun, Xingchu Meng, Wei Zhang, Kai
Wang, Bin Wu, Shanni Li, Hong Qin, and Chao Han: Collected data;
Haohao Li: Analyzed data; and Wei Gao and Zhuolun Song: Wrote
the manuscript.
ORCID
Zhuolun Song  https://orcid.org/0000-0001-5101-3950
Kai Wang  https://orcid.org/0000-0003-3699-2913
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How to cite this article: Gao W, Song Z, Ma N, et al. Utility of
neonatal donors in pediatric liver transplantation: A single‐
center experience. Pediatr Transplant. 2019;e13396. https​://
doi.org/10.1111/petr.13396​