==== Front Surg Case Rep Surg Case Rep Surgical Case Reports 2198-7793 Springer Berlin Heidelberg Berlin/Heidelberg 33315167 1092 10.1186/s40792-020-01092-5 Case Report Biliary atresia in a preterm and extremely low birth weight infant: a case report and literature review Kawano Yuki y_kawano@pedsurg.med.kyushu-u.ac.jp Yoshimaru Koichiro yosimaru@pedsurg.med.kyushu-u.ac.jp Uchida Yasuyuki yasucchii_88@yahoo.co.jp Kajihara Keisuke kay.kajihara@gmail.com Toriigahara Yukihiro trghr.ykhr@live.jp Shirai Takeshi shiraitk@med.kyushu-u.ac.jp Takahashi Yoshiaki yoshiaki@pedsurg.med.kyushu-u.ac.jp http://orcid.org/0000-0002-4937-3890Matsuura Toshiharu matsuura@pedsurg.med.kyushu-u.ac.jp grid.177174.30000 0001 2242 4849Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan 14 12 2020 14 12 2020 12 2020 6 32114 10 2020 2 12 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background Biliary atresia in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants is rarely reported, and the optimal timing of Kasai portoenterostomy (KPE) in these cases remains unclear. Case presentation We report a case of biliary atresia in a preterm female infant of 24 weeks of gestation who weighed 824 g. She underwent exploratory laparotomy and intraoperative cholangiography at 58 days of age (weight, 1336 g). Despite the diagnosis of biliary atresia with a type I cyst, we could only perform gallbladder drainage at that time due to the unstable intraoperative condition. While we waited for her body weight to increase, KPE was performed at 122 days of age (corrected age: 16 days), when the patient weighed 2296 g. Although she initially became jaundice-free, her liver function deteriorated due to cholangitis, and she developed decompensated cholestatic liver cirrhosis. Living donor liver transplantation was successfully performed at 117 days after KPE, and the postoperative course was uneventful. The timing of KPE is difficult to determine and a review of the relevant literature revealed that a poor prognosis in VLBW and ELBW infants with BA. Conclusions Early KPE and careful postoperative follow-up, including liver transplantation is important for the improvement of outcomes. Keywords Biliary atresiaPretermVery low birth weightExtremely low birth weightKasai portoenterostomyissue-copyright-statement© The Author(s) 2020 ==== Body Background Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of neonates that affects the intra- and extrahepatic bile ducts [1]. While the etiology remains unclear, BA is the most common cause of end-stage liver disease and is also the most frequent indication for liver transplantation (LT) in children [2, 3]. Preterm birth has been reported to be a poor prognostic factor in patients with BA [4, 5]. Although some studies have demonstrated the incidence and outcomes of BA in preterm infants, few studies have focused on BA in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. We herein report a case of BA in an ELBW preterm infant born at 24 weeks of gestation. Case presentation A female preterm infant weighing 824 g was born to a 37-year-old woman at 24 6/7 weeks of gestational age (GA) by induced delivery due to chorioamnionitis. Because of bradycardia and unstable respiration, endotracheal intubation was performed immediately after birth, and surfactant was administered under the diagnosis of respiratory distress syndrome (RDS). The Apgar score was 3 at 1 min, 4 at 5 min. After admission to the NICU, the patient was put on mechanical ventilator support. At 4 days of age, a patent ductus arteriosus (PDA) was noted on echocardiography. Cardiac failure due to refractory PDA worsened in spite of the administration of catecholamine and diuretics. Therefore, PDA ligation was carried out at 24 days of age. At 15 days of age, mild hyperbilirubinemia with total bilirubin level of 3.9 mg/dL and a direct bilirubin level of 2.8 mg/dL was noted. Ursodeoxycholic acid (UDCA) and Inchinkoto (traditional Japanese herbal medicine) were administered; however, the conjugated hyperbilirubinemia worsened, and acholic stool was noted at 30 days of age. Abdominal ultrasonography showed a cystic structure at the porta hepatis with a diameter of 6.8 mm (Fig. 1); we therefore suspected BA with a type I cyst or congenital biliary dilatation (CBD). Since exploratory laparotomy (EL) and intraoperative cholangiography (IC) were essential for making a definitive diagnosis as early as possible, the operation was performed at 58 days of age, when the patient weighed 1336 g. During the operation, the liver was soft (Fig. 2a), and IC showed a cystic common bile duct that had no communication with the duodenum, with the intrahepatic ductules showing a cloudy pattern (Fig. 2b). These findings indicated BA with a type I cyst. Although we had initially planned to perform KPE for BA sequentially, we could only perform gallbladder drainage because the patient’s vital signs worsened during the operation. Since there were no significant bleeding or other intraoperative complications, the patient’s immaturity was considered to be the cause of this unstable condition.Fig. 1 Ultrasonography at 37 days of age showed a biliary cyst at the porta hepatis (arrow) Fig. 2 Intraoperative findings at 58 days of age (exploratory laparotomy and cholangiography). a The liver (arrowhead) was still soft. A drainage tube (arrow) was placed in the gallbladder. b Cholangiography revealed a cystic common bile duct (arrow) that had no communication with the duodenum and a cloudy pattern of intrahepatic ductules (circle) After surgery, the color of the fluid drained from the gall bladder was yellowish, and the serum bilirubin level had improved but was not normal, which indicated that cyst-jejunostomy would be ineffective and that Kasai portoenterostomy (KPE) was necessary. We decided to wait for the patient to gain weight and to maintain her general condition. She was extubated at 72 days of age. At 122 days of age (corrected age: 16 days), we performed KPE, with the patient weighing 2296 g. The liver had become firm and cirrhotic (Fig. 3), and portoenterostomy with Roux-en-Y reconstruction was completed without complications. The examination of a liver biopsy revealed bridging fibrosis and cholestasis. The postoperative course was good, and prednisolone was administered from postoperative day (POD) 7 to 31 in accordance with our institution’s routine practice [6]. The serum bilirubin level normalized at POD 27. The patient’s body weight successfully increased (Fig. 4).Fig. 3 Intraoperative findings at 122 days of age (Kasai portoenterostomy). The liver (arrowhead) was firm and cirrhotic. The arrow indicates the common bile duct Fig. 4 The trend in body weight. PDA patent ductus arteriosus, IC intraoperative cholangiography, KPE Kasai portoenterostomy, LT liver transplantation Although a jaundice-free status was initially achieved, the serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels began to increase following the development of cholangitis at 157 days of age (POD 35). Secondary prednisolone therapy was performed; however, the liver function continued to worsen (Fig. 5). Cholestasis, increasing ascites, coagulopathy, and gastrointestinal bleeding were noted subsequently with a pediatric end-stage liver disease (PELD) score 26 and Child–Pugh class C. At 221 days of age (corrected age: 133 days, 117 days after KPE), we performed living donor liver transplantation, with the patient weighing 4106 g. The donor was the patient's mother, who was 38 years of age and whose blood type was identical. The graft was a segment 2 (S2) monosegment graft and the graft-to-recipient weight ratio was 3.23%. Post-transplantation management was conducted as described in our previous report [7]. The postoperative course was uneventful, and the serum bilirubin and liver function profiles normalized by the first postoperative month. Currently, at 14 months after LT, the patient is well and shows a normal liver function with relatively good growth in height (-1.7 SD) and weight (-0.9 SD).Fig. 5 The trends in total bilirubin and PT-%. PDA patent ductus arteriosus, IC intraoperative cholangiography, KPE Kasai portoenterostomy, LT liver transplantation, PSL prednisolone Discussion BA is a rare disease with an incidence of 1 in 8000–15,000 live births [1, 8]. According to the Japanese Biliary Atresia Registry (JBAR), 3,362 BA patients were identified in Japan from 1989 to 2017. Among them there were only 30 cases (0.89%) whose birth weight was less than 1500 g [9, 10]. Since these patients were rarely reported, the clinical course and therapeutic strategy remain unclear. We reported a case with a birth weight of 824 g, which is the lowest weight recorded for a BA patient in Japan. In the present case, despite diagnosing the patient with BA by cholangiography at 58 days of age, we could not perform radical surgery at the time due to the unstable intraoperative condition. To determine the timing of KPE, we had to consider weight gain, the stabilization of the cardiac and respiratory condition, and the progress of treatment for PDA and RDS. We then performed KPE at 122 days of age (corrected age: 16 days). Eventually, the patient required LT due to the development of biliary cirrhosis at 3 months after KPE. Preterm birth is reported to be a poor prognostic factor in BA; however, the exact mechanism remains unclear [4, 5, 11]. In general, the preoperative prognostic factors of KPE are the age at the operation, the presence of the biliary atresia splenic malformation (BASM) syndrome, liver histology, and the anatomic pattern of the bile ducts [12–14]. Most reports indicate that operating at an early age improves the prognosis [4, 12, 14]. Some studies have also investigated the ideal timing of KPE in preterm BA patients. Iwasaki et al. [15] recommended that surgery be performed by a corrected age of 60 days in preterm infants. Jiao et al. [4] also indicated, based on a retrospective study of 34 preterm BA patients, that KPE at a chronological age of ≤ 90 days and a corrected age of ≤ 60 days provided a good prognosis. On the other hand, a study of BA in preterm infants in Taiwan [11], which used the national registry system data, demonstrated that the mean corrected age at the time of KPE was 32.2 days (chronological age: 71.8 days) and that the native liver survival rate of preterm BA patients at 18 months of age was significantly lower than that of term infants (50% vs. 72.7%). This result suggests that the prognosis of preterm BA patients is poor, even if KPE is performed within a corrected age of 60 days. Because few studies focused on BA in VLBW and ELBW infants, a review of the relevant literature was performed using PubMed and Ichushi-Web (a search engine for Japanese literature) to identify the characteristics and prognosis of these cases. Our search yielded 8 cases in the relevant English and Japanese literature; these cases and the present case are summarized in Table 1 [16–20]. All cases involved preterm birth, and the mean birth weight was 1123.8 g. Three cases were ELBW infants; our case had the lowest birth weight and was the only surviving ELBW infant among these reports. One case underwent primary LT, and the other seven underwent KPE. The mean body weight at KPE was 2385.2 g, probably because—in many of the cases—the operation was deferred empirically until a weight gain of 2000–2500 g was achieved. Although six cases underwent KPE within the corrected age of 60 days, five (83.3%) required subsequent LT in this review. The native liver survival rate of VLBW and ELBW infants with BA was found to be much poorer in comparison to general preterm BA patients, even though the KPE was performed within the corrected age of 60 days. Careful follow-up and avoiding delays in LT are necessary to improve the outcome.Table 1 Cases of BA in VLBW and ELBW infants reported in the English and Japanese literature Case Authors Year Gestational age at birth (weeks) Sex Birth weight (g) Chronological age at KPE (days) Corrected age at KPE (days)a Body weight at KPE (g) Type of BA Clinical course 1 Chen et al. [16] 2007 31 M 1375 51 (GA 38 2/7) 2164 III LT at 7 months after KPE 2 Hashimoto et al. [17] 2007 27 F 834 187 96 2660 III-b1-ν Died at 36 days after KPE 3 Fallon et al. [18] 2013 27 M 1090 107 20 N/A N/A LT at 2 years of age 4 Sanmoto et al. [19] 2017 33 F 1425 37 (GA 38 5/7) 2151 I-b1-β Native liver survival at 5 months after KPE 5 Miyatake et al. [20] 2018 31 F 940 102 44 2346 N/A LT at 9 months after KPE Died at 1 month after LT 6 29 F 1200 N/A N/A N/A N/A Primary LT at 7 months of age 7 33 F 1302 70 21 2694 N/A LT at 8 months after KPE 8 Present case 2020 24 F 824 122 16 2296 I-cyst LT at 3 months after KPE KPE Kasai portoenterostomy, BA biliary atresia, LT liver transplantation, GA gestational age aWhen the corrected age at KPE is a negative value, the gestational age (in weeks) is shown The poor prognosis of KPE may imply the insufficiency of the criterion of the corrected age of 60 days. Given that recent studies have suggested that BA only manifests after loss of the protective physiology of the mother and placenta [2], the chronological age at KPE may reflect the prognosis more accurately rather than the corrected age. Actually, in our case, despite the liver being relatively soft at the first surgery (EL and IC) at 58 days of age, it became cirrhotic by the time of the second surgery (KPE) at 122 days of age. On the other hand, however, when KPE is performed too early, before sufficient weight gain can be achieved is associated with an increased risk of intraoperative and postoperative complications. Further studies with a larger sample size, which focus on BA in VLBW and ELBW infants should be performed to clarify the optimal timing of KPE in these cases. Conclusions We described the clinical course and prognosis of BA in VLBW and ELBW infants. It is preferable to perform KPE earlier; however, the optimal timing is difficult to determine due to their complicated clinical condition. Because of the poor prognosis of KPE, careful postoperative follow-up, including LT, are important for improving patient outcomes. Abbreviations BABiliary atresia LTLiver transplantation VLBWVery low birth weight ELBWExtremely low birth weight GAGestational age RDSRespiratory distress syndrome PDAPatent ductus arteriosus UDCAUrsodeoxycholic acid CBDCongenital biliary dilatation ELExploratory laparotomy ICIntraoperative cholangiography KPEKasai portoenterostomy PODPostoperative day ASTAspartate aminotransferase ALTAlanine aminotransferase PTProthrombin time PELDPediatric end-stage liver disease JBARJapanese Biliary Atresia Registry BASMBiliary atresia splenic malformation Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Acknowledgements We thank Brian Quinn (editor-in-chief, Japan Medical Communication, Inc., Fukuoka, Japan) for his assistance with the reading and editing of the manuscript. Authors’ contributions YK and KY contributed to the writing. TM contributed to the critical review and revision. YK, KY, YU, KK, YT, TS, YT, and TM performed the surgery and postoperative management. All authors read and approved the final manuscript. Funding The authors received no funding related to the manuscript. Availability of data and materials The datasets supporting the conclusions of this article are included within the article. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. ==== Refs References 1. Davenport M Biliary atresia Lancet 2009 374 1704 1713 10.1016/S0140-6736(09)60946-6 19914515 2. Bezerra JA Wells RG Mack CL Karpen SJ Hoofnagle JH Doo E Biliary atresia: clinical and research challenges for the twenty-first century Hepatology 2018 68 3 1163 1173 10.1002/hep.29905 29604222 3. Scheenstra R Peeters PMGJ Verkade HJ Gouw ASH Graft fibrosis after pediatric liver transplantation: ten years of follow-up Hepatology 2009 49 3 880 886 10.1002/hep.22686 19101912 4. Jiao C Yu K Li D Fu K Wang P He Y A retrospective study of the ideal operation time for preterm biliary atresia patients Pediatr Surg Int 2019 35 6 679 684 10.1007/s00383-019-04464-7 30805663 5. Van Wessel DBE Boere T Hulzebos CV De Kleine RHJ Verkade HJ Hulscher JBF Preterm infants with biliary atresia: a nationwide cohort analysis from the Netherlands J Pediatr Gastroenterol Nutr 2017 65 4 370 374 10.1097/MPG.0000000000001692 28727655 6. Nio M Muraji T Multicenter randomized trial of postoperative corticosteroid therapy for biliary atresia Pediatr Surg Int 2013 29 11 1091 1095 10.1007/s00383-013-3377-6 23989522 7. Yoshimaru K Matsuura T Hayashida M Kinoshita Y Takahashi Y Yanagi Y Transient hyperphosphatasemia after pediatric liver transplantation Pediatr Int 2016 58 8 726 731 10.1111/ped.12914 26754078 8. Nio M Japanese Biliary Atresia Registry Pediatr Surg Int 2017 33 12 1319 1325 10.1007/s00383-017-4160-x 29039049 9. Japanese Biliary Atresia Society Japanese biliary atresia registry 2017 J Jpn Soc Pediatr Surg 2019 55 2 291 297 10. 10Japanese Biliary Atresia Society. Japanese Biliary Atresia Registry 2017. https://jbas.net/registration. Accessed 1 May 2020. 11. Chiu CY Chen PH Chan CF Chang MH Wu TC Biliary atresia in preterm infants in Taiwan: a nationwide survey J Pediatr 2013 163 1 100 103 10.1016/j.jpeds.2012.12.085 23414661 12. Song Z Dong R Shen Z Chen G Yang Y Zheng S Surgical outcome and etiologic heterogeneity of infants with biliary atresia who received Kasai operation less than 60 days after birth: a retrospective study Medicine 2017 96 26 1 5 10.1097/MD.0000000000007267 13. Wong KKY Chung PHY Chan IHY Lan LCL Tam PKH Performing Kasai portoenterostomy beyond 60 days of life is not necessarily associated with a worse outcome J Pediatr Gastroenterol Nutr 2010 51 5 631 634 10.1097/MPG.0b013e3181e8e194 20818266 14. Townsend MR Jaber A Abi Nader H Eid SM Schwarz K Factors associated with timing and adverse outcomes in patients with biliary atresia undergoing Kasai hepatoportoenterostomy J Pediat 2018 199 237 242 10.1016/j.jpeds.2018.04.001 29773306 15. Iwasaki M Hashimoto K Kamimura R Ikeda Y Kobayashi H Hanafusa T Clinical diagnosis and surgical management for cholestasis in premature infant J Jpn Soc Pediatr Surg 2006 42 470 479 16. Chen HW Hsu WM Chang MH Chen CY Chou HC Tsao PN Embryonic biliary atresia in a very-low-birth-weight premature infant J Formos Med Assoc 2007 106 1 78 81 10.1016/S0929-6646(09)60220-5 17282975 17. Hashimoto K Nakamura K Ikeda Y Sokoda T Furukawa O Shindan chiryō ni kuryoshita tandōheisashō no chōteishussei taijūji no ichirei [A case of biliary atresia in an extremely low birth weight infant with difficult diagnosis and treatment] Perinatal Medicine 2007 37 149 153 18. Fallon SC Chang S Finegold MJ Karpen SJ Brandt ML Discordant presentation of biliary atresia in premature monozygotic twins J Pediatr Gastroenterol Nutr 2013 57 4 e22 e23 10.1097/MPG.0b013e31826a1044 22847464 19. Sanmoto Y Masumoto K Sakamoto N Aoyama T Fujii S Chiba F A case of a very low birth weight infant diagnosed as having biliary atresia Jpn Soc Pediatr Surg 2017 53 958 961 20. Miyatake H Sakamoto R Nakamura K Five cases of preterm infant with biliary atresia J Jpn Pediatr Soc 2018 122 1474 1480