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2009 John Wiley & Sons A/S.

Clin Transplant 2010: 24: 550556 DOI: 10.1111/j.1399-0012.2009.01123.x

Risk factors for portal vein complications in


pediatric living donor liver transplantation
Shibasaki S, Taniguchi M, Shimamura T, Suzuki T, Yamashita K, Susumu Shibasakia, Masahiko
Wakayama K, Hirokata G, Ohta M, Kamiyama T, Matsushita M, Taniguchia, Tsuyoshi
Furukawa H, Todo S. Risk factors for portal vein complications in Shimamurab, Tomomi Suzukic,
pediatric living donor liver transplantation. Kenichiro Yamashitad, Kenji
Clin Transplant 2010: 24: 550556. 2009 John Wiley & Sons A/S. Wakayamaa, Gentaro Hirokataa,
Minoru Ohtab, Toshiya
Abstract: Background: Portal vein (PV) complications in pediatric living
Kamiyamaa, Michiaki Matsushitaa,
donor liver transplantation (LDLT) are often asymptomatic in the early
stages after transplantation and can be serious enough to lead to graft Hiroyuki Furukawac and Satoru
failure. There have been few reports on risk factors for PV complications in Todoa
a
LDLT. The aim of this study is to investigate the inuence of hepatic inow Department of General Surgery, bDivision of
upon PV complications and to predict patients at risk for these complica- Organ Transplantation, cDepartment of Organ
tions. Transplantation and Regeneration and
d
Material/method: From 1997 to 2008, 46 pediatric patients underwent Department of Molecular Surgery, Graduate
LDLT at our center. Portal venous and hepatic arterial ows and PV School of Medicine, Hokkaido University,
diameter were analyzed. Sapporo, Japan
Results: PV complications were identied in seven patients (15.2%) and
occurred at a younger age and lower weight. As a result of appropriate
treatment, none of the patients suered graft failure. Analysis of the 46 Key words: liver transplantation living donor
patients and 27 patients under two yr of age indentied smaller PV diameter pediatric portal vein complications
in recipient and larger discrepancy of PV diameter as risk factors. Portal
Corresponding author: Masahiko Taniguchi, MD,
venous ow tended to be low, in contrast to hepatic arterial ow, which
Department of General Surgery, Graduate
tended to be high.
School of Medicine, Hokkaido University, N-15,
Conclusion: PV size strongly inuences PV complications. Other factors
W-7, Kita-ku, Sapporo 060-8638, Japan.
such as younger age, low portal venous ow, and high hepatic arterial ow
Tel.: +81 11 706 7062; fax: +81 11 706 7064;
may be risk factors for PV complications.
e-mail: tonny@isis.ocn.ne.jp

Accepted for publication 25 August 2009

Pediatric liver transplantation is one of the most tions are often asymptomatic; in fact, 64% of such
eective modalities for treatment of pediatric end- asymptomatic cases were detected by abdominal
stage liver diseases. Since living donor liver ultrasound screening (13). In a few cases with few
transplantation (LDLT) was rst performed by symptoms, these complications can become extre-
Raia in 1988 in Brazil (1), pediatric LDLT has been mely serious, as indicated by reports of a mortality
accepted as an alternative to orthotopic liver rate of 5.230% and a graft loss rate of 7.935%
transplantation (OLT) because of the shortage of (6, 8, 13, 14). Thus, careful follow-up leading to
donor grafts. In actuality, outcomes for pediatric earlier discovery and earlier treatment is crucial to
end-stage liver diseases have improved dramati- preventing graft loss.
cally: the patient survival rates in pediatric LDLT However, there are few reports on risk factors
at ve and 10 yr have reached 8298% (25) and for PV complications in pediatric LDLT. A more
7782% (3, 4), and the graft survival rates at 5 and rigorous follow-up can be performed by clarifying
10 yr have reached 8189% (4, 5) and 75% (4). risk factors for these complications. The aim of this
Recently, reports of portal vein (PV) complica- study is to investigate what inuences the occur-
tions in pediatric LDLT have increased, occurring rence of PV complications and to predict patients
at an incidence of 827% (510) when compared to with a high risk of such complications in pediatric
1.83% in adult recipients (11, 12). PV complica- LDLT.

550
Risk factors for PVC in pediatric LDLT

thereafter every three months. If any abnormal


Materials and methods
signs were found, specic tests such as angiography
Patients were performed. All decisions on diagnosis and
treatment were made according to our algorithm for
Subjects were individuals involved in 46 pediatric
PV complications (Fig. 1).
(under 18 yr of age) LDLTs at this center from
September 1997 to March 2008. All grafts were
harvested from healthy adult living donors who Surgical technique
were fully informed and who donated voluntarily.
When the graft was implanted, the donor hepatic vein
The donors were 41 parents (14 fathers and 27
was anastomosed to a new diamond-shaped orice on
mothers), three grandparents (one grandfather and
the front of the inferior vena cava, below the conu-
two grandmothers), one sister, and one aunt. The
ence of the recipients middle hepatic vein and left
harvested grafts were 29 lateral lobes, seven left
hepatic vein. Next, PV anastomosis was performed
lobes, and 10 left lobes with the middle hepatic vein
using continuous Prolene 6-0 suture with making
and one right lobe. The mean ratio of the graft
growth factor. The hepatic vein was then unclamped
volume to standard liver volume was
and portal reperfusion began. After reperfusion,
74.1 27.9% (mean SD range, 36.1133.7).
hepatic artery anastomosis and bile duct reconstruc-
Patients by sex broke down into 19 males and 27
tion, using a Roux-en-Y loop, were performed.
females with an age of 4.29 4.93 yr
There were four methods of PV reconstruction.
(mean SD range, 0.317) and body weight of
End-to-end anastomosis, anastomosis of the graft
16.4 13.5 kg (mean SD range, 4.154). The
PV and the trunk of the recipients PV, was
indications for liver transplant are shown in
performed in 35 cases. Branch patch anastomosis,
Table 1. Biliary atresia was the most frequent
anastomosis of the graft PV to the bifurcation of
indication for liver transplant and was noted in 31
the right and left branches of the recipients PV,
cases (67.4%).
was performed in one case. Conuence anastomo-
Early complications were dened as the onset of
sis, anastomosis of the graft PV to the conuence
PV complications within the rst one month after
of the recipients superior mesenteric vein and
LDLT, and late complications were dened as onset
splenic vein, was performed in ve cases. Inter-
after that point. The mean duration from sur-
posed harvested vein graft anastomosis, anasto-
gery to the onset of late complications was
mosis using a graft harvested from the donor, was
10.4 8.3 months. Pre-operative recipient and
performed in ve cases; in two cases, the external
donor PV diameter were measured by pre-operative
jugular vein was used; in two, the gonadal vein was
abdominal contrast-enhanced computed tomogra-
used; and in one, the inferior mesenteric vein was
phy (CT). Intraoperative ow of the hepatic artery
used. Prophylactic anticoagulant therapy was not
(HA) and PV was measured with an ultrasonic
routinely administered.
transit ow meter. Routine post-operative protocols
for CT and abdominal ultrasonography (US) were
performed as follows: CT, two wk and one to three, Statistics
and six months after transplantation and thereafter
Patients with and without PV complications were
every three months; US, twice daily until one wk
compared using the MannWhitney U test. In
after transplantation, once daily until two wk after
addition, patients were limited to those under
transplantation, then, as in the case of CT, one to
two yr of age, and the same comparison was made.
three, and six months after transplantation, and
Factors with a signicant dierence were compared
Table 1. Indications for liver transplantation
using Fishers exact test with the smallest p-value
serving as the cuto point. Statistical signicance
Cholestatic conditions (n=37) was denoted by p < 0.05.
Biliary atresia 31
Progressive familiar intrahepatic cholestasis 2
Hepatic failure of unknown origin 4 Results
Metabolic disease (n=7)
Wilsons disease 2 PV complications were identied in seven patients
Glycogen storage disease 1 (15.9%). Early PV thrombosis occurred in one,
Ornithine transcarbamylase deficiency 2 early PV stenosis in one, late stenosis in four, and
Metylmaronic acidemia 1 late occlusion in one. Of the seven cases, ve were
Hyperoxaluria 1
diagnosed by routine CT or US, while two were
Neoplasm (n=2)
Hepatoblastoma 2 discovered because of an increase in ascites. Of the
seven patients, four had a decreased platelet count.

551
Shibasaki et al.

Fig. 1. Algorithm for follow-up and treatment of PV stenosis (A) and occlusion (B). PV patency in the early period following
transplantation is usually evaluated by routine US and CE-CT. Additional CE-CT is performed if an abnormality such as decreased
or lack of PV ow is detected by US. If PV stenosis or occlusion is suspected, angiography is performed to diagnose PV compli-
cations. Late-phase PV patency is followed by routine US and CE-CT. If suspicions arise, angiography is performed to make a
decision. With regard to treatment, there are some dierences between the early and late periods following transplantation. Re-
anastomosis is considered in acute stenotic cases that occur within seven d after living donor liver transplantation. In contrast, PTA is
the rst-line therapy for late-stage stenosis. Despite the controversy over long-term patency, stent replacement is considered in cases
that are refractory to repeat balloon dilation. Because early-stage PV occlusion is almost always caused by thrombosis and leads to
acute graft failure, an emergency procedure such as thrombectomy or reconstruction is necessary to prevent graft loss. On the other
hand, because late-stage PV occlusion occurs gradually and is likely to develop collaterals, anticoagulant therapy is the rst choice,
and retransplantation is considered in cases with PV hypertension. US, abdominal ultrasonography; CE-CT, contrast-enhanced
abdominal computed tomography; PTA, percutaneous transhepatic angioplasty; POD, post-operative day.

552
Risk factors for PVC in pediatric LDLT

The levels of transaminase were close to normal complications (Table 3). In one of the cases where
levels in all seven patients. an interposed graft was used, the native PV was so
Results for risk factors are shown in Table 2. PV hypoplastic that anastomosis required four at-
complications occurred at a younger age and lower tempts; the paternal external jugular vein was
weight. With regard to other factors, pre-operative ultimately used in this case. In another complicated
PV diameter in recipient and pre-operative ratio of case, the maternal gonadal vein was used.
donorrecipient PV diameter were strongly related In one case of early PV thrombosis, re-anasto-
to the occurrence of PV complications. Low portal mosis of the PV was performed using the external
venous ow and high hepatic arterial ow after jugular vein from the father as an interposition
reperfusion also caused a high occurrence of PV graft. In one case of late occlusion, occlusion was
complications. In other words, the ratio of portal complete but the PV developed collaterals, so only
venous ow to hepatic arterial ow in patients with anticoagulant therapy was performed. All ve
PV complications was signicantly smaller than in cases of stenosis, both early and late, were
patients without PV complications. Analysis lim- improved by repeated transhepatic balloon dila-
ited to patients under two yr of age revealed that a tion. The patients in these seven cases are all
smaller PV size and a higher ratio of donor currently alive (Table 4).
recipient PV diameter cause a high occurrence of
complications. In terms of the cuto point, signif-
Discussion
icant dierences were found with a pre-operative
PV diameter in recipient 4 mm (p < 0.001), This study has demonstrated that PV complica-
pre-operative ratio of donorrecipient PV diameter tions in pediatric LDLT occurred more often with
2.3 (p < 0.001), portal venous ow after reper- a smaller PV size, even in younger age recipients.
fusion 150 mL/min/100 g (p = 0.046), and he- A small PV diameter is thought to relate to great
patic arterial ow after reperfusion 50 mL/min/ discrepancy in PV diameter between donor and
100 g (p = 0.046). With regard to multivariate recipient and low portal venous ow, which may
analysis, there were no signicant dierences represent potential risk factors for PV complica-
because of the small sample size. In terms of the tions.
type of anastomosis, conuence and interposed There have been several reports on being young
graft anastomosis had a high occurrence of PV and having a lower body weight as risk factors for

Table 2. Univariate analysis of risk factors for portal vein (PV) complications

Non-complications
Complications Non-complications group under two -yr-old,
group, (n = 7) group, (n = 39) p-Value (n = 24) p-Value

Age (yr) 0.99 0.41 4.9 5.1 0.043 0.94 0.40 0.739
Sex (M/F) 2/5 17/22 6/12
Height (cm) 67.7 5.6 95.3 34.3 0.023 67.8 6.5 0.856
Weight (kg) 7.5 1.4 18.0 14.1 0.011 7.8 2.0 0.449
BMI 16.4 1.2 17.1 2.1 0.383 16.9 2.5 0.809
Biliary atresia 6 25 18
Child-Pugh-Turcott score 7.0 1.5 7.7 2.2 0.189 7.9 1.9 0.173
Operation time (min) 638.0 224.0 808.5 226.2 0.031 690.9 174.2 0.250
Bleeding (mL) 307.1 224.4 1450.0 1946.9 0.004 623.3 600.4 0.074
Cold ischemic time (min) 36.7 19.6 55.4 39.7 0.119 49.4 47.2 0.525
Warm ischemic time (min) 33.3 7.3 42.0 19.7 0.076 43.6 29.0 0.304
PV anasto-time (min) 14.0 3.7 16.2 9.2 0.433 17.8 12.9 0.380
Donors age (yr) 28.4 3.3 35.7 9.9 0.027 31.8 8.8 0.304
The ratio of graft volume to standard liver volume (%) 83.7 12.0 72.4 30.0 0.194 93.6 27.1 0.397
HA (mm) 3.4 0.53 3.7 1.0 0.717 3.3 0.7 0.505
PV diameter (mm) 3.7 0.95 7.4 2.6 0.0002 5.8 1.4 0.027
Donors PV diameter (mm) 9.4 1.6 9.3 1.5 0.766 9.1 1.7 0.525
PV size ratio of donor to recipient 2.7 0.92 1.4 0.49 0.0003 1.6 0.4 0.0022
PV flow (mL/100 g/min) 150.0 73.1 239.0 100.0 0.026 189.8 70.0 0.204
HA flow (mL/100 g/min) 50.7 23.5 30.6 18.4 0.022 34.1 18.5 0.090
PV/HA flow ratio 3.8 2.8 12.7 14.2 0.0078 8.5 6.9 0.069

HA, hepatic artery; PV, portal vein.

553
Shibasaki et al.

Table 3. Methods of portal vein reconstruction tis in biliary atresia are thought to shrink the
smaller PV and increase the risk of PV complica-
N Complication %
tions. In the current study, complications devel-
End-to-end 35 3 8.6 oped in 19.4% of biliary atresia cases, which is
Bifurcation 1 0 0 slightly higher than the 16.5% reported by Chardot
Confluence 5 2 40 et al. (22).
Interposition 5 2 40 Portal venous ow is thought to be another risk
factor. With regard to portal venous ow after
reconstruction, Bueno et al. (25) reported that low
PV complications in pediatric LDLT (1520). At portal venous ow contributed to the resultant
this facility, patients who were younger or had a thrombosis in OLT, and Cheng et al. (15) reported
lower body weight had a higher occurrence of PV that slow portal venous velocity was predictive of
complications as well. The reason for this is thought intraoperative portal vein thrombosis. In contrast,
to be because of the small PV diameter and hepatic arterial ow tended to increase in the
discrepancy in the size of the diameter between the current study like it did in the report by Bueno
donor and recipient. In the current study, PV et al. (25). This is thought to be because the blood
complications occurred more often in cases of a ow supplied to the liver is constant; a reduced
smaller PV diameter and greater discrepancy in size. portal venous ow gives rise to a corresponding
Cheng et al. (15) reported that a pre-operative increase in hepatic arterial circulation. There is a
PV diameter of <4 mm was associated with a high report that noted a signicant increase in hepatic
risk for intraoperative portal vein occlusion. A arterial ow after the temporary occlusion of the
smaller PV diameter would reasonably lead to a portal vein (26). Poor portal venous ow is thought
greater size discrepancy between the donor and to be caused by serious liver cirrhosis existing pre-
recipient PV, so the risk of developing PV compli- operatively because of biliary atresia, the eects of
cations is naturally expected to rise as well. That portal inow escaping through collateral path-
said, there has only been one case report (21) and ways, and the eects of a hypoplastic PV. We did
one study (22) on size discrepancy in OLT. A PV is not directly prove that the pre-operative PV ow
expected to be smaller in patients that are younger was poor by measuring it before reperfusion.
or have a lower body weight; in the current study, However, in hypoplastic PV cases, a stenotic PV
there were dierences between the group with PV that lasts for years before transplantation conse-
complications and that without PV complications quently leads to a compensatory increase in HA
even when looking only at patients under two yr of ow. This condition persists even after transplan-
age. Besides age, biliary atresia is a potential cause tation. We consider the compensatory increase to
of a smaller PV. Diem et al. (23) reported that be a risk factor for post-transplant PV complica-
19.5% of biliary atresia cases had PV hypoplasia. tions. However, there are doubts over whether late
Additionally, Saad et al. (24) performed a patho- PV complications are directly aected by portal
logical study of native PV in resected livers in venous ow because the ow was not periodically
LDLT; they reported that only 20% were normal measured. Whether decreased portal venous ow
or had changed little, but up to 43% had severe persisted as it did post-operatively is unknown.
brosis. Based on these facts, biliary atresia and a The current study did suggest that decreased portal
smaller PV are closely related. In other words, venous ow, when induced an increased hepatic
severe portal inammation and repeated cholangi- arterial ow, might itself represent a high risk of

Table 4. Prognosis for patients with portal vein (PV) complications. The left side of the follow-up duration indicates the time since diagnosis, while the right side
indicates the time since final treatment was performed (months)

Age Opportunity PV Follow-up Final


Case (months) Type Onset of diagnosis Therapy patency duration (M) outcome

1 14 Stenosis 10 M Late CT PTA 3 Patent 61/41 Alive


2 6 Stenosis 10 M Late CT PTA 2 Patent 64/61 Alive
3 10 Thrombosis 7d Acute US Reoperation Patent 69/69 Alive
4 6 Stenosis 1M Acute Ascitis PTA 5 Patent 41/16 Alive
5 11 Stenosis 2M Late Ascitis PTA 2 Patent 42/41 Alive
6 20 Occlusion 6M Late CT Anticoagulant Occlusion 19/19 Alive
7 15 Stenosis 24 M Late CT PTA 1 Patent 14/14 Alive

M, month; PTA, percutaneous transhepatic angioplasty; CT, computed tomography; US, ultrasonography.

554
Risk factors for PVC in pediatric LDLT

complications. Thus, ow at reperfusion may serve mortality, so during reconstruction, increasing the
as an indicator for the onset of PV complications. portal venous ow and minimizing the discrepancy
Crucial responses to these risk factors are in portal vein size are crucial to preventing these
increasing portal venous ow by clamping collat- complications. Additionally, high-risk groups such
eral pathways and devising methods of reconstruc- as those mentioned above should be closely followed
tion that reduce the size discrepancy. Someda et al. and PV complications should be detected early on.
(27) reported that ligation of the collateral path-
ways was eective at improving poor portal venous
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