Editors’
ChoiceORIGINAL PAPER

Nagoya J. Med. Sci. 83. 765–771, 2021
doi:10.18999/nagjms.83.4.765

Long-term outcomes of the partial splenectomy for
hypersplenism after portoenterostomy of patientswith biliary atresia
Takahisa Tainaka, Akinari Hinoki, Yujiro Tanaka, Chiyoe Shirota,
Wataru Sumida, Kazuki Yokota, Satoshi Makita, Kazuo Oshima,
Hizuru Amano, Aitaro Takimoto, Yoko Kano and Hiroo Uchida
Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

ABSTRACT
Massive splenomegaly and hypersplenism in patients with biliary atresia after Kasai portoenterostomy
were treated with partial splenic embolization or total splenectomy. We performed partial splenectomy
to reduce the complications of partial splenic embolization and avoid overwhelming post-splenectomy
infection. This study aimed to evaluate the long-term effects of partial splenectomy for hypersplenism on
postoperative liver and spleen function in patients with biliary atresia. Among jaundice-free patients withbiliary atresia who underwent Kasai portoenterostomy between January 1992 and December 2012, 15
underwent partial splenectomy for massive splenomegaly and hypersplenism at our institution. Changes in
the laboratory data 10 years post partial splenectomy were retrospectively investigated, and these along withthe latest data were measured. A total of four patients (27%) required living-donor liver transplantation
after partial splenectomy, a proportion similar to those who did not undergo partial splenectomy. Comparedto the preoperative baseline, the platelet counts were significantly higher at 1 and 3 years after surgery(p < 0.05). Aspartic aminotransferase-to-platelet ratio index was significantly lower at 1, 7, and 10 years
after partial splenectomy (p < 0.05). No further surgeries were required for hypersplenism after partial
splenectomy over 10 years, and there were no cases of overwhelming post-splenectomy infection afterpartial splenectomy. Partial splenectomy is safe and effective for the treatment of hypersplenism with biliaryatresia over a long time period. It could be considered as an alternative to partial splenic embolization as
it can suppress hypersplenism for a long time and induces fewer postoperative complications.
Keywords: biliary atresia, partial splenectomy, portal hypertension, splenomegaly, hypersplenism
Abbreviations:
BA: biliary atresia
PSE: partial splenic embolization
PS: partial splenectomy
AST: aspartic aminotransferase
APRI: aspartic aminotransferase-to-platelet ratio index
This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Received: December 23, 2020; accepted: March 19, 2021
Corresponding Author: Uchida Hiroo, MD, PhD
Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho,Showa-ku, Nagoya 466-8550, Japan
Tel: +81-52-744-2959, Fax: +81-52-744-2980, E-mail: hiro2013@med.nagoya-u.ac.jp
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INTRODUCTION
Biliary atresia (BA), also known as progressive obliterative cholangiopathy, is a rare cholestatic
disease of unknown etiology resulting in neonatal biliary obstruction and jaundice.1 The prognosisof patients with BA has improved since the introduction of Kasai portoenterostomy in 1959.2,3Portal hypertension and its associated variceal hemorrhage are common and fatal complications ininfants with BA.1,4,5 BA is a progressive disease, even in the absence of jaundice; thus, majorityof patients will develop cirrhosis and portal hypertension. Approximately 49–63% of patients
have clinical evidence of portal hypertension as demonstrated by ascites, variceal bleeding,hepatopulmonary syndrome (HPS), splenomegaly, and thrombocytopenia. 4 While liver failure
requires liver transplantation, in patients without hepatic insufficiency, the risks related to portal
hypertension and hypersplenism justify the symptomatic treatments. Splenomegaly and hypersplenism in patients with biliary atresia have often been treated using partial splenic embolization(PSE) or total splenectomy.6,7,8 Complications such as fever and abdominal abscess after PSE
were frequent.9 Total splenectomy is known to increase overwhelming post-splenectomy infection(OPSI) caused by encapsulated bacteria such as streptococcus pneumoniae using a capsule.10 We
performed partial splenectomy (PS) to reduce these complications of PSE, normalize splenic
function, and avoid OPSI. The long-term effect on the liver and spleen function of BA after PS
has not received much scholarly attention. The purpose of this study was to evaluate the effectof PS on postoperative liver and spleen function and the long-term outcomes in patients with BA.

PATIENTS AND METHODS
Study sample
Among the patients with BA who underwent Kasai portoenterostomy between January 1992
and December 2012, patients who were jaundice-free and had undergone PS for massive splenomegaly and hypersplenism were enrolled in the study. Hypersplenism with thrombocytopenia
was defined as a platelet count ≤100,000/μl.
Surgical techniqueLaparotomy was performed through a left abdominal transverse incision under general anesthesia without performing platelet transfusion before and during the surgery. First, the spleen was
turned out of the wound to expose the splenic hilum. The splenic artery and vein are normallybranched into three; hence, the splenic artery and vein were ligated from the side of the lower
pole at the splenic hilar. At this time, extra care was taken to not damage the splenic vein.
If the vein is damaged, it will be difficult to assess the anatomy of the splenic hilum becauseof bleeding, and the risk of damaging the splenic vein increases. Regarding the ligation of theblood vessels, the color of the spleen becomes black (Fig. 1a). The splenic artery and vein of
the upper spleen are preserved. The border of the middle and lower poles of the spleen whosecolor had changed was marked with an electric scalpel, and the spleen was cut off using an
ultrasonic surgical aspirator system along it. Moreover, it was necessary to observe the bloodflow of the left upper spleen using an ultrasound device. After the splenectomy was completed(Fig. 1b), we applied fibrin glue to the stump of the spleen. The volume to be resected wasapproximately 70% of the total spleen. The collateral circulation around the spleen was notblocked. We were careful not to form portal vein thrombi by administering heparin while paying
attention to the increase in platelet count because there had been cases where platelets increased
rapidly after surgery.

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Partial splenectomy for BA patients

Fig. 1 Intraoperative images
Fig. 1a: The color of the spleen becomes black with the ligation of the blood vessels.
Fig. 1b: Partial splenectomy was completed.

Changes in the laboratory data such as total bilirubin, aspartic aminotransferase (AST),
serum albumin, white blood cell (WBC) counts, hemoglobin, platelet counts, and aspartic
aminotransferase-to-platelet ratio index (APRI) were retrospectively investigated (before PS at 1,
3, 5, 7, and 10 years after surgery). APRI has been reported as an noninvasive marker which
can predict hepatic fibrosis and liver cirrhosis in patients with chronic hepatitis C.11 In addition,
the latest laboratory data were measured.
The Wilcoxon rank-sum test for continuous data, Fisher exact test for categorical data, andDunn test for the change in data over a period of time with the preoperative values as controls
were used in the statistical analysis. P values <0.05 were considered as statistically significant.
The study protocol was approved by hospital medical ethics committees (approval numbers
2019-0420).

RESULTS
During the study period, 82 patients underwent Kasai portoenterostomy for BA, and 64
patients were jaundice-free. Fifteen out of these 64 patients underwent PS for treatment of
massive splenomegaly and hypersplenism. Four patients, who had been previously treated withsplenorenal shunt, were included because they showed hypersplenism following splenorenal
shunt surgery. The patients’ characteristics are summarized in Table 1. The median age at Kasai
portoenterostomy was 71 days (47–82). The median age at the PS was 7 years (3.4–10), themedian surgery time was 260 min (204–390), and the median amount of bleeding was 194 ml(52–1072). The resection rate was 50–75%. Four patients required blood transfusion, and postoperative complications occurred in two cases. One patient had liver damage and was relieved byconservative treatment. Another patient had portal vein thrombosis; therefore, liver transplantation
was performed as planned. There was no case of variceal bleeding after PS. A total of four
patients (27%) underwent living-donor liver transplantation after PS (four cases over 3 years after

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Takahisa Tainaka et al

hepatic portoenterostomy). In contrast, eight (16%) patients who were jaundice-free after hepatic
portoenterostomy without PS required living-donor liver transplantation (one case within 1 year,
three cases from 1 year to 3 years, and four cases over 3 years after Kasai portoenterostomy). PS
did not cause an increase in liver transplantation in comparison with patients who underwent PS.

Table 1

Patient demographics

Biliary atresia with partial splenectomy (n=15)
Male/Female

8:7

Age at Kasai’s operation (day)71 (47–82)

Biliary atresia typeType I

1

Type III

14

Laboratory data at Kasai’s operation
TB(mg/dl)7.0 (5.2–10.8)

AST(IU/L)

181 (145–516)

ALT(IU/L)

139 (79.8–411)

Jaundice free

15 (100%)

Age at partial splenectomy (year)

7.0 (3.4–10)

Laboratory data at PS
WBC(103/μl)

3.4 (2.8–4.1)

Hb(g/dl)

10.5 (9.0–11.4)

Platelet (104/μl)

6.6 (3.9–8.9)

Operation time (min)260 (204–390)

Amount of blood loss (ml)194 (52–1072)

Follow-up period after partial splenectomy (year)

14.1 (10.4–14.6)

Changes in the laboratory data after PS are shown in Fig 2. The patient number at 1, 3, 5,
7, and 10 years after PS were 15, 13, 13, 11, and 11, respectively. The values of total bilirubinand serum albumin remained within normal limits after PS surgery. Aspartic aminotransferase(AST) was 83 preoperative and 91, 96, 79, 61, and 53 with no significant differences at 1, 3,
5, 7, and 10 years after PS, respectively. WBC counts were higher after PS, but the differenceswere not significant. Hb levels tended to increase over time (pre-op: 11.4; 1 year: 11.4; 3 years:
11.8; 5 years: 12.9; 7 years: 13.1; and 10 years: 14.5), but the differences were not statisticallysignificant. The platelet counts were 6.6 before surgery and 14, 12, 9.4, 9.2, and 10 at 1, 3, 5,
7, and 10 years after PS, respectively. Significant increases in the platelet counts were observed
at 1 and 3 years after surgery (p < 0.05). The value of APRI was significantly decreased at 1,
7, and 10 years after surgery (7.7, 5.0, 6.4, respectively; p < 0.05). No further surgeries wererequired for hypersplenism after PS over 10 years. Additionally, there were no cases exhibiting
increased susceptibility to infection or OPSI after PS.

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Partial splenectomy for BA patients

Fig. 2

Changes in laboratory data after the PS (Total bilirubin, AST, Albumin, WBC, Hb,
Platelet counts, APRI)*p<0.05, Dunn test.

DISCUSSION
Kasai’s portoenterostomy in BA patients aims to improve the rate of survival without livertransplantation by restoring bile flow.12,13 BA is a progressive disease, even in jaundice-freepatients with native liver; thus, majority of patients will develop cirrhosis and portal hypertension.4 Patients with BA after portoenterostomy had clinical evidence of portal hypertension asdemonstrated by ascites, variceal bleeding, hepatopulmonary syndrome (HPS), splenomegaly, and/or thrombocytopenia. Variceal hemorrhage occurs in 24–55% of patients.14,15 Hypersplenism is amajor complication of BA. Nonetheless, the incidence, prevalence, and long-term outcomes ofhypersplenism in patients with BA have not been studied.
Liver failure with BA requires liver transplantation. In patients without hepatic failure, the risks
are related to portal hypertension, and hypersplenism justifies the symptomatic measures. Severe
hypersplenism is often refractory to treatment with PSE or shunt surgery. PSE was introduced
as an alternative to splenectomy to avoid the risk of OPSI and to achieve splenic reduction. In
patients with BA, the procedure was successful during the early follow-up period. As a result,hypersplenism was controlled, and the frequency in addition to the severity of bleeding fromthe esophageal varices reduced.6 Porter reported that the splenic arterial flows decrease whereas
the hepatic and superior mesenteric arterial flows increase after PSE.16 PSE proved to have along-lasting efficacy in controlling hypersplenism.6,7 because 70% of the patients had maintained
platelet counts greater than 100,000/μl for more than 5 years after PSE. Brandt reported that
10 of 13 patients had no signs of hypersplenism after an average follow-up of more 3 years.9

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Takahisa Tainaka et al

Moreover, we reported that the total bilirubin reduced because of the decreasing turnover inthe red blood cell and liver enzyme did not change.17 However, early complications after PSE
such as fever, abdominal pain, abscess surrounding spleen, lung atelectasis, and prolonged ileus
were frequent.9 Furthermore, there were no reports of treatment outcomes after PSE observed
for more than 10 years. Our operative PS aimed for satisfactory outcomes such as PSE and to
reduce postoperative inflammatory complications due to necrosis of the embolized spleen. After
PS procedure, we had no patients suffering from severe infection. PS requires a strict surgicalprocedure; however, it can be easily achieved. The postoperative course was uneventful in majorityof the patients with cystic fibrosis-related liver diseases.18 We noted one postoperative complicationas portal vein thrombosis. Portal vein thrombosis after PSE has been reported to occur in certain
cases in adults.19 After splenectomy, this complication was often described, indicating that wemust pay more attention to thrombosis.
APRI, an indicator of portal vein pressure and hepatic fibrosis,20 remained low over time
although the liver enzymes remained almost unchanged after PS. This study showed that PS
had a long-term positive effect on portal hypertension.21,22 The value of the latest APRI as anindex of the hepatic fibrosis are relatively low.20 There were no cases of variceal bleeding after
PS, indicating a clinical effect. Variceal hemorrhage was ameliorated in all patients after PSE,9and it is expected to have almost the same effect. The native liver survival rate is about 70%
after PS. Four patients required liver transplantation for liver failure in two, gastrointestinal
bleeding in one, and recurrent cholangitis in another. These suggest that PS is useful in termsof improving the patient’s QOL.
Central shunt surgeries with splenic preservation are successful for reversing mild to moderate
hypersplenism23; nevertheless, massive splenomegaly is often refractory to such procedures.24
In our four cases, splenorenal shunt could not improve hypersplenism; hence, we performed
PS. Even if the shunt surgery achieved good results in patients without any hepatic failure,they had to follow a low-protein diet. Twenty percent of the patients with BA had hepatic
encephalopathy.25 Therefore, PS, which could not decrease the flow of the portal vein, is anextremely safe procedure and a good surgical indication for splenomegaly and hypersplenism
after Kasai portoenterostomy. PS preserved anatomic and vascular relation of the hepatosplenic
axis and was not an obstacle to a subsequent liver transplantation; this was confirmed in ourliver transplantation patients. In this study, we described the long-term significant outcomes of
PS for more than 10 years, which has never been reported.
Several limitations to this study must be considered. First, the number cases in this study was
small because BA is a rare disease. Second, this study is retrospective and does not have anappropriate control group with PSE. However, we could show fairly long-term outcomes after PS.
In conclusion, PS is safe and effective for treatment of hypersplenism with BA over a longtime period. It could be considered as an alternative for PSE as it could suppress hypersplenism
for a long time and induces fewer postoperative complications.

CONFLICT OF INTEREST STATEMENT
There are no conflicts of interest to disclose.

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