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Background: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children., Methods: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography., Results: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002)., Conclusion: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT., Methods: All children receiving a first LT from October 1990 to October 2010 in our center were included., Results: Included 151 children (boys 55.0%), with a mean age of 4.8 ± 4.8 years, and a mean weight of 17.9 ± 14.4 kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10 kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision., Conclusion: Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest disclosures to make., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: The appropriate timing of liver transplantation (LT) in patients with biliary atresia (BA) who survived with their native livers until adolescence remains controversial. The liver-spleen volume ratio (LSR) has been reported to be efficacious in predicting the prognosis of chronic liver disease. We investigated whether LSR could predict long-term native liver prognosis and serve as an indication for LT in patients with BA., Methods: Patients with BA who survived with their native liver until the age of 15 years were included. These patients were classified into 2 groups. The unfavorable prognosis group included patients who underwent or were awaiting LT or developed complications such as refractory cholangitis or gastrointestinal bleeding due to esophagogastric or intestinal varices. The favorable prognosis group included patients who survived with their native liver without complications. We compared the 2 groups regarding LSR, hematological, and histologic data., Results: Of 19 patients, 8 were in the unfavorable prognosis group, and 11 were in the favorable prognosis group. LSR was significantly lower in the unfavorable prognosis group (P = .009). Analysis of the receiver operating characteristic curve showed that the area under the curve of the LSR was 0.891, which was higher than the area under the curve of liver fibrosis markers. The optimal LSR cut-off value for predicting poor native liver prognosis was 1.97, with a sensitivity of 75.0% and a specificity of 87.5%., Conclusions: The LSR reflects splenomegaly and liver atrophy. The LSR might be a reliable predictor of native liver prognosis and could guide decisions about LT in patients with BA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pediatric living-donor liver transplantation (LDLT) has become one of the most effective therapies for pediatric end-stage liver diseases. We aim to investigate the risk factors for intra-operative portal vein thrombosis (PVT) and the short- and long-term outcomes in children post LDLT., Methods: This was a retrospective analysis from 584 cases of biliary atresia (BA) patients who had undergone LDLT from January 2014 to December 2019 at our hospital. Patients were divided into PVT and non-PVT groups according to the occurrence of PVT during LDLT., Results: The median age of recipients at transplantation was 7.22 (quartiles, 6.03, 9.50) months, the incidence of intra-operative PVT was 5.31% (31/584). The independent risk factors for intra-operative PVT were the diameter of the recipient's PV not greater than 4 mm and a higher ratio of graft-to-recipient PV diameter. The cumulative survival rates of grafts and recipients were 93.5% and 93.5% in the PVT group, and 94.9% and 95.3% in the non-PVT group, respectively, without significant difference. The recovery of graft function was similar in recipients with or without interposed graft vessel (IGV). However, the incidence of PV stenosis was higher in recipients with IGV after LDLT., Conclusion: Intra-operative PVT is a common complication in pediatric LDLT, but an excellent prognosis can be achieved by appropriate and individualized surgical treatment. We noted that intra-operative PVT did not affect the survival rates of grafts and recipients, but there was a higher incidence of PV complications after LDLT., Level of Evidence: Ⅲ., Competing Interests: Declaration of competing interests The authors declare no conflicts of interest. We would like to thank all authors who contributed to this research and all authors are in agreement with the content of the manuscript. We certify that we have participated sufficiently in the work to take public responsibility for the experimental design and method, and the analysis and interpretation of the data., (Copyright © 2022. Published by Elsevier Inc.)

Objective: This study further explored the wind direction correlation analysis between serum levels of TGF- β 1 and VEGF and liver function assessment in children with biliary atresia., Methods: A total of 62 children with biliary atresia (BA) who received surgical treatment in our hospital from October 2020 to October 2021 were selected as the research objects (BA group), and 50 normal healthy children who received routine physical examination in our hospital during the same period were selected as blank control group. Outcome measures included postoperative total bilirubin levels and conjugality of enrolled patients. Bilirubin level, unbound bilirubin level, serum transforming growth factor-beta-1 (TGF- β 1), vascular endothelial growth factor (VEGF), liver function indicators albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other observation indicators were included. All data in this study were collected and analyzed by SPSS 23.0 software, and t -test was performed., Results: The serum levels of TGF- β 1, VEGF, ALT, AST, GGT, and liver hardness were significantly higher in children with jaundice than those without jaundice, and the serum ALB level was significantly lower than that in children without jaundice ( P < 0.05). The levels of TGF- β 1 and VEGF in BA group were positively correlated with the levels of ALT, AST, GGT, and liver hardness ( P < 0.05) but negatively correlated with the level of ALB ( P < 0.05)., Conclusion: The levels of serum TGF- β 1 and VEGF in children with biliary atresia have a certain risk correlation with liver function damage, which will become a research focus on the mechanism of liver fibrosis in the diagnosis and treatment of biliary atresia in children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dongzhe Chang et al.)

This study aimed to determine whether circulating levels of clusterin (CLU), an extracellular chaperone implicated in cholestatic and fibrotic processes, are associated with clinical parameters of post-operative BA patients and could serve as a BA biomarker. Ninety-six BA patients and 56 healthy controls were recruited. Circulating CLU levels were measured using enzyme-linked immunosorbent assay. Circulating CLU levels were significantly reduced in BA patients - especially those with worse outcomes including jaundice, severe liver fibrosis, and late-stage of hepatic dysfunction. Multivariate linear regression analysis revealed that circulating CLU levels were negatively associated with outcome parameters indicating jaundice status, degree of fibrosis, and liver dysfunction, but positively correlated with serum albumin and platelet number of BA patients. Lower circulating CLU levels were considerably associated with poor survival of post-operative BA patients. Receiver-operating characteristic curve analysis demonstrated a diagnostic value of circulating CLU as a non-invasive indicator for poor outcomes of BA patients (AUC = 0.85), with a sensitivity of 81.5% and a specificity of 73.5%. All findings indicate that reduced circulating CLU might reflect poor outcomes of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Background: Intrahepatic cystic lesion (ICL) is a common complication for biliary atresia post-Kasai portoenterostomy. The purpose of this study was to review the cases in our hospital and assess the correlation between characteristics of ICL and clinical outcomes., Methods: We retrospectively analyzed 787 cases of biliary atresia from 2012 to 2016. Demographics, clinical details, and postoperative outcomes were reviewed., Results: A total of 76 patients were diagnosed with ICLs using ultrasound post-Kasai procedure, and the incidence was 9.7%. Preoperative characteristics showed no significant differences between ICL (+) and ICL (-) groups. Nearly 70% (53/76) of the patients with ICLs had a history of cholangitis. The 2-year native liver survival rate was 60.4% for those with a history of cholangitis and 87% for those without (P = 0.017). Further analysis showed that the 2-year native liver survival rate was 42.9% for those diagnosed within 3 months post-Kasai procedure, 54.2% for those diagnosed between 3 and 6 months, and 80.0% for those diagnosed beyond 6 months (P = 0.002), while no significance was observed for type (P = 0.094) or site (P = 0.406) of ICL., Conclusion: Patients with ICLs had a high incidence of cholangitis. The prognosis was closely related with the history of cholangitis and the onset time of ICLs., Level of Evidence: Level II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The incidence and several risk factors of biliary complication (BC) following pediatric liver transplantation (LT) are widely known, but data on long-term outcomes and management is limited. This retrospective study aimed to investigate the incidence, associated risk factors, management, and outcomes of early and late BC in pediatric LT., Methods: This study enrolled 134 pediatric patients (< 18 years old) who underwent LT at a tertiary care center in Taiwan between January 2001 and December 2015. Diagnosis of BC was based on clinical, biochemical, and radiologic examinations. Clinical data and chart records were reviewed and compared between the groups., Results: Among the 134 children, 21 children (15.7%) had BC after LT. Nine children had early complications, including leakage plus stricture (n = 2), stricture only (n = 2), and leakage only (n = 5). Twelve children had late BC; all of whom had anastomotic stricture. Of the 21 patients with BC, 11 patients (52.4%) were treated without surgery. The median time of first treatment for BC was 6.5 months (range, 11 days to 6.2 years). Five of the 9 patients with early complications and two of the 12 patients with late complications died of biliary tract infection. The major risk factors of BC in pediatric LT were (1) recipient age > 2 years, (2) Kasai portoenterostomy revision, and (3) hepatic artery thrombosis., Conclusions: Several risk factors of BC in pediatric LT were identified. Children with early BC appeared to have relatively unfavorable outcomes. However, late BC treated by either radiological or surgical methods appeared to have a relatively good long-term prognosis.

Background: Liver transplantation (LT) is an excellent treatment option for patients with biliary atresia (BA) who fail portoenterostomy surgery. LT is also increasingly performed in patients with metabolic liver diseases. This study compared the outcomes in pediatric patients who underwent LT for metabolic liver diseases and BA., Basic Procedures: Data from 237 pediatric patients who underwent primary LT at Seoul National University Hospital from 1988 to 2015, including 33 with metabolic liver diseases and 135 with BA, were retrospectively analyzed., Main Findings: Compared with children with BA, children with metabolic liver diseases were significantly older at the time of LT (121.3 vs. 37.3 months; P < 0.001), and had lower Child-Pugh (7.1 vs. 8.4; P = 0.010) and Pediatric End-stage Liver Disease (6.5 vs. 12.8; P = 0.042) scores. Overall survival rates were similar (87.8% vs. 90.8%; P = 0.402), but hepatic artery (HA) complications were significantly more frequent in children with metabolic liver diseases (12.1% vs. 1.5%; P = 0.014)., Principal Conclusion: Despite similar overall survival, children with metabolic liver diseases had a higher rate of HA complications., Type of Submission: Original article, Case control study, Retrospective., Evidence Level: III., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Comparative studies and large-scale case series that confirm the advantages of laparoscopy in children with hepatobiliary diseases are scarce, and the use of laparoscopy remains a matter of debate. This article reviews the current literature on the role of laparoscopic and robotic surgery in pediatric patients with choledochal cyst, biliary atresia, gallbladder diseases, and hepatobiliary malignancies. Studies were identified through a search of the MEDLINE database. Laparoscopy may be beneficial for resection of choledochal cyst and cholecystectomy. However, more data are required before recommendations on the use of minimally invasive techniques for other hepatobiliary conditions can be published., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients., Methods: One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography., Results: BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P < 0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1 ± 2.1 vs. 27.9 ± 2.5 ng/mL, P < 0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r = 0.491, P < 0.001), alanine aminotransferase (r = 0.448, P < 0.001), total bilirubin (r = 0.303, P = 0.002), alkaline phosphatase (r = 0.414, P < 0.001), and liver stiffness values (r = 0.455, P < 0.001). There was a negative correlation between serum HSP70 and serum albumin (r = -0.434, P = 0.001)., Conclusion: Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

Objectives: Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes., Methods: Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL)., Results: Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P < 0.001)., Conclusions: Parents and families appear to be resilient in coping with serious infant illness. Infant diagnosis other than biliary atresia and parental perceptions of high impact of the illness on the family are indicators of negative emotional outcomes for infants with serious liver disease. Psychosocial interventions for infants with chronic illness should target reducing the impact of illness on the family.

We aim to provide a panorama of liver donation and transplantation in Poland, where each year around 300 liver transplantations from deceased donors and 20 liver fragment transplantations from living donors are performed. This means about 9 transplantations per population of 1 million. Each year, the number of deceased donors reaches more than 500. In more than 50% of cases, livers are used. The law allows liver procurement from living donors. Until the end of 2013, liver fragments were recovered from 236 living donors and transplanted mainly to pediatric recipients (n = 232). A living-donor registry was created to monitor and assess the health condition of donors. The range of the national waiting list and allocation is nationwide. It is managed with the use of the Web tool www.rejestry.net. There are 2 modes of recipient referral: "urgent" and "elective." Allocation is either patient oriented and center oriented. Disease groups, which comprise the most frequent indications for transplantation in adults, include the cirrhosis group (48%), in which the highest number of procedures was performed for patients with hepatitis C virus (24%); alcohol-induced cirrhosis (14%); alcohol-induced hepatitis (8%), and hepatitis B virus cirrhosis (7%). Among pediatric recipients, the most frequent indications were congenital cholestatic diseases, which made up 38% of all transplantation indications. The results of liver transplantations are collected in the national transplant register. The 1-year graft and recipient survival with deceased donor transplantation are 81% and 84% and with living donor transplantation 86% and 89%. The 5-year graft and recipient survival in deceased donor transplantation are 69% and 73%, and in living donor transplantation are 80% and 83%., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to characterize the clinical outcomes of children and adolescents who achieved survival of more than 10 years following liver transplantation (LT) in a single center in Korea. From June 1996 to October 2003, 57 pediatric LTs were performed. The medical records of 44 patients who had survived more than 10 years were reviewed retrospectively. Median age of patients at LT was 0.8 years. Forty-one patients received living donor LT, and three patients received deceased donor LT. Biliary atresia was the most common indication (65.9%). Thirty-five patients were on tacrolimus monotherapy at 10 years post-LT with a mean trough level of 2.73 ng/ml, and five patients were maintaining stable graft function without any immunosuppression. There were no patients receiving antihypertensive medication and one case of diabetes mellitus. Renal dysfunction was seen in two patients (4.5%), while none required renal replacement therapy. Mean height z-score prior to LT was -1.35 and at 10 years post-transplant was 0.05. Good linear growth was sustained in this cohort throughout the 10 years, approaching the 50th percentile. Also, there were remarkably low incidences of renal dysfunction and patients requiring medications for glycemic or hypertensive control, all hallmarks of continued use of immunosuppressive agents., (© 2015 Steunstichting ESOT.)

In living-donor liver transplantation, graft selection is especially important for the safety of the live donor and an acceptable outcome for the recipient. The essential medical requirements for living liver donation at Jikei University Hospital are as follows: an adult aged 65 years or younger, in good general condition, with partial liver volume of more than 35% of the standard liver volume (SLV) for the recipient, and without severe liver steatosis. Based on our criteria, we performed 13 living-donor liver transplantations between 2007 and 2013, including 1 retransplantation. Three cases were outside our standard donor criteria, including age (18 and 66 years) and 33% graft volume (GV) to SLV ratio for the recipient on preoperative volumetry using computed tomography. In 2 cases, the actual GV to SLV ratio at transplantation was less than 35%. Median postoperative hospital stay was 11 days for the donors, and 29 days for the recipients. All donors returned to their preoperative status, and all recipients were discharged in good condition. Our medical requirements for living liver donation seem to be acceptable because of the good outcome.

Background: Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful portoenterostomy (PE) on native liver histology remain unclear., Aims: We assessed changes in native liver histology after a successful PE in relation to liver function and clinical outcomes., Methods: In total, 70 native liver biopsies of 44 biliary atresia patients were obtained at PE (n=30), 4.2 years after successful PE (n=23) and 1.1 years after failed PE (n=17), and reviewed for cholestasis, fibrosis, inflammation, and cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor livers served as controls., Results: After a successful PE [serum bilirubin 11 (2 to 35) μmol/L at biopsy], histologic native liver cholestasis completely resolved in 83% of the patients and portal inflammation significantly decreased. Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects, respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of the patients, associated with the presence of portal hypertension, and correlated with serum-conjugated bilirubin (r=0.601, P=0.002), bile duct proliferation (r=0.657, P=0.001), and CK7 positivity (r=0.657, P=0.001). Aspartate transferase to platelet ratio index predicted native liver fibrosis and development of esophageal varices. The degree of fibrosis and portal inflammation at PE were unrelated to native liver survival., Conclusions: Despite resolution of cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7 immunostaining, and fibrosis persist after successful PE. Fibrosis is associated with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity (chronic cholestasis), and development of portal hypertension.

Background and Study Aims: Since the introduction of liver transplantation (LTx) in children suffering from liver failure in 1963, many centres around the world have offered this service to children that have no other alternative. The aim of this retrospective study is to analyse the results of paediatric liver transplant in Kuwait over the last decade., Patients and Methods: A retrospective chart review was done involving paediatric patients during the time period of 1995-2004. The information collected included patient demographics, indications for liver transplantation, survival of both patient and allograft, and complications., Results: A total of 16 cases were found and analysed. The mean age was 3.6years (ranged 5months-17years). There were nine boys and seven girls. The most common indications for LTx were biliary atresia and metabolic liver disease. All the liver transplants were done abroad. There were totally nine deceased donor and seven living related cases. The complications were acute cellular rejection in five, hypertension in two, biliary complications in four, cytomegalovirus (CMV) infection in three and post lymphoproliferative disease in two cases. All but one patient are presently alive., Conclusion: The above information demonstrates that LTx in Kuwati children is safe and improves the quality of life for those that would otherwise have no other alternative., (Copyright © 2012. Published by Elsevier Ltd.)

Purpose: To clarify the significance of intrahepatic cystic lesions (ICLs) after Kasai procedure for biliary atresia (BA), we reviewed the BA patients with special reference to the shape of ICLs., Methods: For the last two decades, 75 cases have been followed up at our institution. The patients were divided into two groups: ICLs (+) with ICL and ICLs (-) without ICL. Seventeen cases of ICLs (+) were divided into two categories: the round type and the multiple-bead type. A poor prognosis was defined as mortality or the need for liver transplantation (LT)., Results: The ratio of round to multiple-bead types was 6:11. The percentage of poor prognoses with ICLs (+) and ICLs (-) was 47 and 53 %, respectively. The percentage of poor prognoses with round and multiple-bead types was 27 and 83 %, respectively (p < 0.05). In cases of ICLs (+), an LT was required because of hepatic deterioration in all three of the round types, and intractable cholangitis in all five of the multiple-bead types (p < 0.05)., Conclusion: The long-term prognosis of BAs after the Kasai procedure does not necessarily depend on the development of ICLs per se, but on their shape.

Background: : Depletion of beta-carotene (b-c) has not been extensively studied in children with chronic cholestatic liver disease., Patients and Methods: : We assessed b-c serum concentration in 53 children with cholestatic liver disease: 19 patients operated on for biliary atresia, 12 with Alagille syndrome, and 22 with progressive familial intrahepatic cholestasis. To test b-c absorption, 6 children with chronic cholestasis received a load of 10 mg b-c/kg body weight., Results: : We found decreased b-c concentrations in 45 patients. The absorption of b-c was not detectable in 5 of 6 children studied., Conclusions: : b-c depletion is a common problem of chronic cholestatic liver disease in childhood that can be attributed to disturbed intestinal absorption.

Extrahepatic biliary atresia (EHBA) is the most common indication for liver transplantation in infants and children. Congenital malformations associated with EHBA are common and present in about 9%-37%. We describe a case of a child who received a left lobe liver transplant for syndromic EHBA., ((c) 2009 John Wiley & Sons A/S.)

Growth retardation is one of the most prominent consequences of childhood cholestatic liver diseases. The pathogenesis of malnutrition is multifactorial and includes reduced calorie intake, fat malabsorption, abnormal protein metabolism, and increased energy expenditure. Poor growth is a typical feature of biliary atresia, cystic fibrosis, progressive familial intrahepatic cholestasis and Alagille syndrome. In some of these features it is not only directly related to impaired nutrient absorption. Liver transplantation is required if liver disease progresses to liver failure - improved nutritional status is achieved within weeks after surgery. Still, patients with Alagille syndrome present with only slight catch-up growth after transplantation, while patients with PFIC and biliary atresia grow significantly.,

Alcohol sclerotherapy is useful for the treatment of biliary cutaneous fistulas in patients who have undergone hepatic resection. The same principle can be applied for transplant recipients with isolated draining biliary ducts. Percutaneous therapy of isolated draining biliary ducts with absolute alcohol (ie, 100% ethanol) was successfully performed in a 7-year-old patient who had undergone orthotopic liver transplantation. The increasing use of segmental living and split cadaveric liver grafts, with the subsequent increase risk in biliary complications, necessitates more efficient therapy for isolated draining bile ducts.

Background: Biliary atresia (BA) is a cholestatic disease of unknown etiology. It has recently been suggested that graft-vs-host disease caused by microchimerism is an etiology in the development of autoimmune disease. Moreover, the liver is a frequent target organ of graft-vs-host disease. The aim of this study is to identify the presence and extent of maternal microchimerism and to determine whether it plays a role in the etiology of BA., Methods: The liver biopsy specimens of 6 male patients with BA (BA group) and 6 males with other liver diseases (non-BA group) were assayed for X- and Y-chromosome using fluorescent in situ hybridization. The cells with 2 sex chromosomes in the nuclei were counted. Cells with 1 X- and 1 Y-chromosomes were considered to be host cells, and those with 2 X-chromosome were considered to be of maternal origin., Results: The frequency of cells with XX chromosomes per 1000 host cells in the BA group and the non-BA group were 3.00 +/- 0.75 and 0.99 +/- 0.50, respectively (P = .005). Moreover, the age at the time of biopsy did not affect the number of chimeric cells., Conclusion: The presence of female cells in the liver of male patients with BA was significantly higher than in males with other liver disease. Maternal microchimerism is therefore suggested to contribute to the pathogenesis of BA.

A pseudotumor, giant regenerative nodule, or macroregenerative nodule is an unusual benign hepatic lesion in biliary atresia (BA) patients. This tumor may mimic malignant transformation and may preclude liver transplantation (LT). The clinical and imaging surveillance of patients after the Kasai procedure is therefore an important aspect of management of BA patients. Our objective is to report our experience and describe the incidence, imaging, and pathologic features of pseudotumors in BA patients awaiting LT. From August 1990 to December 2006, 133 LTs for BA were performed. Five (3.8%; 4 female, 1 male) patients were diagnosed with pseudotumor. The patients' records were reviewed. The diagnostic imaging modalities used were abdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI). Histologic confirmation of the lesions was obtained in all cases. All underwent the Kasai operation in early infancy. Six of 7 lesions in 4 of 5 patients were demonstrated by pretransplant imaging. Two of 7 tumors were detected by US. Five of 7 lesions were detected by CT, and 5 of 7 lesions were demonstrated by MRI. In 1 patient, the lesion was not seen in the US, CT, or MRI but was found during surgery and confirmed by histology. An additional tumor was found incidentally during histologic examination in a patient previously diagnosed to have 2 tumors by CT and MRI. In another patient diagnosed to have 2 tumors on imaging, pathology revealed only a single tumor. In conclusion, although unusual, pseudotumor should be included in the differential diagnosis of liver masses in BA children., ((c) 2007 AASLD.)

Aim: The aim of this study was to evaluate the impact of mild and moderate intrapulmonary shunting (IPS) in children with end-stage liver disease (ESLD) undergoing liver transplantation., Materials and Methods: A total of 73 patients (38 male, 35 female; mean age 31.5 +/- 35.2 months, range 6-180 months) with ESLD and subsequent liver transplantation were enrolled. Based on contrast echocardiography, patients without IPS were assigned to group 1 (n = 57), and patients with mild or moderate IPS were assigned to group 2 (n = 17). The preoperative age, body weight, O(2) saturation, length of hospital stay, duration of mechanical ventilation, postoperative complications, and 1-year survival rate were compared between groups., Results: The overall incidence of IPS and 1-year survival rate were 23.3% (17/73) and 96% (70/73), respectively. There were significant differences between group 1 and group 2 patients regarding age at transplant (35.9 vs. 16.6 months, p = 0.002) and body weight (12.6 vs. 8.5 kg, p = 0.002). There were no other statistically significant differences between the two groups., Conclusion: Although children with mild and moderate IPS were younger at the time of transplantation and had significantly lower body weight than those without IPS, the presence of mild and moderate IPS in children with ESLD did not affect the overall outcome of liver transplantation.

Background: Intrahepatic cystic lesions develop after hepatic portoenterostomy in some patients with biliary atresia and have been regarded as an indication of poor prognosis; however, there is confusion about the terminology and concepts of the lesions. We investigated whether the cystic lesions constituted a single entity., Patients and Methods: From 1980 to 2005, we encountered 80 patients with biliary atresia. Abdominal ultrasonography disclosed intrahepatic cystic lesions in 20 (25%) patients after hepatic portoenterostomy. The cystic lesions were analyzed morphologically with radiologic imaging studies and histologically in 13 patients who underwent liver transplantation., Results: Fifteen patients had solitary simple cystic lesions, and 5 patients had multiple continuous oval or beaded lesions. Solitary lesions had a fibrotic cyst wall and lacked epithelia. Continuous lesions had a cyst wall covered with biliary epithelia. Thirteen patients with solitary cysts died or required liver transplantation. In 2 patients with continuous lesions, surgical reboring of the porta hepatis could eliminate cystic lesions and jaundice., Conclusions: Intrahepatic cystic lesions include 2 different conditions. Solitary cysts are retention pseudocysts, which should be referred to as a bile lake, and are associated with poor prognosis. Continuous beaded cysts are dilated bile ducts, which may be reversed. This distinction is important when considering the treatment strategy.

Background: Hepatolithiasis after hepatic portoenterostomy for biliary atresia has been paid little attention, with only 22 reported cases., Patients and Methods: Fifteen patients underwent living-related liver transplantation for biliary atresia after hepatic portoenterostomy in our hospital between 1998 and 2004. The resected livers were examined for the existence and location of hepatolithiasis, composition of the calculi, and bacterial infection of bile. The relation between a history of cholangitis and the presence of hepatolithiasis was analyzed., Results: Intrahepatic calculi were found in 8 (53%) of 15 patients. The calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15 patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis., Conclusions: Hepatolithiasis occurs after hepatic portoenterostomy for biliary atresia more frequently than previously thought. Bile stasis and possibly bile infection are the main causes of calculi formation.

The authors present current status of liver transplantation (LTx) in Poland. Till 2004, 845 LTx were performed: 604 in adults and 241 in children; 71 of them were the living donor LTx. Post-inflammatory cirrhosis in adults and biliary atresia in children were the most common indications for LTx. The results of LTx in Poland are good and comparable with the results published by other centers. The number of available cadaveric grafts is growing and in 2004 achieved an index of harvesting as high as 14,7 per million people.

Background: The result of hepatic portoenterostomy for biliary atresia (BA) has improved, but there are some patients who experience worsened liver function in the long term after one decrease in jaundice owing to portoenterostomy. However, the cause of the liver dysfunction in the long term has not been clearly ascertained., Methods: Five patients (5 to 28 years of age) with BA underwent liver transplantation (LT) because of liver dysfunction after successful portoenterostomy. To clarify the cause of liver dysfunction occurring in the long term, the authors performed a cholangiogram, hepatic venogram, and macroscopic/microscopic examination of the liver just after LT., Results: (1) Macroscopically, the liver could be divided into 3 areas, the hypertrophic, atrophic, and intermediate, with findings between those of the hypertrophic and atrophic areas. (2) The divided areas clearly corresponded to the liver segments. Segment IV was the hypertrophic area in all patients, but segments VI and VII were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic and microscopic findings, the hypertrophic area had near-normal structure with bile ducts. The atrophic area had severe fibrosis and contained only a few bile ducts in the intralobular spaces of liver., Conclusions: It seems that segmental bile drainage must have been established by hepatic portoenterostomy in some patients and that some postoperative patients might have worsened liver function in the long-term follow-up period accompanied with progression of fibrosis and impaired bile drainage. These pathologic changes occur in each liver segment.

Objectives: Extrahepatic biliary atresia (EHBA) is the most common indication for liver transplantation in childhood. Most children who do not undergo transplant are reported to have chronic liver disease and its complications. The aim of this single-center study was to identify children with normal laboratory indices and no clinical evidence of chronic liver disease 10 or more years after Kasai portoenterostomy (KP)., Methods: A retrospective analysis of the medical notes of all children surgically treated at the authors' center between 1979 and 1991 was undertaken. Criteria for inclusion were absence of surgical complications, unremarkable clinical examination, and normal bilirubin, aspartate aminotransferase, albumin, international normalized prothrombin ratio, and platelet count., Results: Of 244 children surgically treated during the observation period, the authors identified 28 (11%) adolescents (14 male) who fulfilled the entry criteria. Their median age was 13.4 years (range, 10.2-22.2 years). Twenty-six with type 3 EHBA had conventional KP, whereas 2 underwent modified operations. The corrective surgery was performed at a median age of 58 days (range, 20-99 days). Median time of complete clearance of jaundice from the date of KP was 75 days (range, 21-339 days). Twelve (43%) patients had history of cholangitis at a median age of 3.4 years. The liver histologic findings were suggestive of mild to moderate fibrosis in 54.2% and cirrhosis in 40.7% of the patients who underwent biopsy. No child had gastrointestinal bleeding during follow-up. Thirteen (46%) patients had an elective esophagogastroduodenoscopy, which was normal in all. Twenty-six (93%) patients were in mainstream education, whereas the remaining two (7%) attended special school because of reasons unrelated to liver disease., Conclusions: A sizable proportion of children with EHBA avoid significant chronic liver disease and its complications 10 years or more after conventional surgical correction and have an excellent quality of life. Their good outcome is not hampered by isolated episodes of ascending cholangitis. Whether or not the residual histologic damage will become symptomatic during their lifetime remains to be established.

The advances made in surgical technique, postoperative care, and immunosuppression during the 1980s have permitted orthotopic liver transplantation (OLT) to evolve into an effective and widely accepted therapy for infants and children with end-stage liver disease. Biliary atresia, a progressive, obliterative disease of the bile ducts, is the most common indication for OLT in children, accounting for approximately 50% of cases. Metabolic liver disease (MLD) accounts for 20% to 25%; other common indications for OLT include fulminant hepatic failure (FHF) and forms of intrahepatic cholestasis. The principal problem associated with the increasing application of OLT is the burden placed on resources, particularly the availability of donor organs. The limited pool of size-matched donor organs has led to the application of a variety of alternatives to address the needs of the pediatric recipient; these include (1) reduced-size liver transplantation, (2) "split-liver" transplantation, and (3) use of living-related organ donors. In view of the impact on overall organ availability, the use of nontransplant options, including liver cell transplantation, especially for FHF and MLD, deserves broader application. Despite the success of transplantation, major challenges in childhood liver transplantation remain, including (1) improved preoperative management to ensure adequate growth, (2) more precise posttransplant management of immunosuppression to ensure graft viability and avoidance of lymphoproliferative disease, (3) earlier recognition of cytomegalovirus and Epstein-Barr virus infection, and (4) provision of services in a more cost-effective manner. The ultimate solution is to prevent liver disease through vaccination and research.

Objective: To assess the results of paediatric liver transplantation in our institution., Methods: From September 1993 to November 1996, 10 living-related liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were performed on 12 children at our hospital. The medical records of the patients were reviewed. All patients suffered from end-stage liver disease resulting from biliary atresia with failed Kasai's operations. Their ages at initial transplantation ranged from 8 months to 11 years. Excluding the 2 older children aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial transplantation., Results: All living donors were discharged on postoperative day 4 to 8 and resumed their previous normal activities. All recipients were alive with normal liver function and growing after a follow-up period of 3-40 months (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had hepatitis of undetermined aetiology and underwent retransplant with a graft from her mother. The graft survival rate was 92%. Postoperative complications included: postoperative bleeding (n = 3), hepatic vein stenosis (n = I), biliary-enteric anastomotic stenosis (n = 3), intestinal perforation (n = I) and portal vein thrombosis (n = I). They were all treated promptly. In all patients, the hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by microvascular technique. There was no hepatic artery thrombosis in our patients., Conclusion: With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in paediatric liver transplantation.

Background: The hepatopulmonary syndrome with profound hypoxemia is a rare but severe complication for children with liver cirrhosis. It can be reversed by liver transplantation (LT), which is now regarded as a good indication. However, previous reports have described cases of transient or fatal deteriorations of intrapulmonary shunting after pediatric liver transplantation with dramatically worsening hypoxemia., Methods and Results: A similar case during and after LT in a 4-year-old girl with severe hepatopulmonary syndrome is described with prompt reversal of hypoxemia by inhaled nitric oxide, which was discontinued definitely until day 14 after LT., Conclusions: During or after LT, worsening hypoxemia may be improved by using inhaled nitric oxide in pediatric patients undergoing liver transplantation for liver cirrhosis and hepatopulmonary syndrome. The mechanisms are unclear, but may involve mismatching lung ventilation-perfusion. However, additional clinical reports are necessary before accepting these results.

Background/aims: Early liver transplantation is crucial in children with liver disease and pulmonary artery hypertension. Some severe pulmonary vascular anomalies associated with portal hypertension disappear after isolated liver transplantation. Evolution of pulmonary artery hypertension due to plexogenic arteriopathy is controversial, as this association is still considered a contraindication to isolated liver transplantation. Outcome of pulmonary hypertension after isolated liver transplantation is reported in three patients with portal hypertension., Methods: After echocardiographic diagnosis, the patients had a complete hemodynamic exploration, and two had a lung biopsy. After liver transplantation, the survivors had echocardiographic follow up and a second hemodynamic exploration., Results: In two children, pulmonary pressures and resistances returned to near-normal values 1 and 6 years after successful isolated liver transplantation. The third patient, with the most severe arteriopathy, had to wait 1 year for a donor, and the attempted transplantation was complicated by ventricular tachycardia; death occurred 2 days after surgery., Conclusions: Liver transplantation can reverse pulmonary artery hypertension due to high pulmonary resistances complicating liver disease with portal hypertension, provided it is carried out at an early stage. Early detection of pulmonary hypertension by systematic echocardiography may thus be crucial in these children with portal hypertension.

An external conduit (stoma) for patients with biliary atresia has been used to prevent postoperative cholangitis. Thirty-two patients with biliary atresia who had hepatic portoenterostomies with external conduits were studied retrospectively with respect to frequency and severity of postoperative cholangitis or stoma bleeding. Changes in their liver enzyme levels, and total bilirubin (TB) levels were measured before and after closure of the stoma. Cholangitis was observed in 20 patients (62.5%), and major hemorrhage from the stoma site was seen in 14 patients (43.8%) prior to closure. Levels of liver enzymes such as glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (gamma-GTP), and alkaline phosphatase (ALP) improved significantly within 1 month after closure of the stoma, and remained low thereafter. The TB concentration was the only liver function that did not change significantly following closure. In summary, the authors do not recommend an external conduit in patients with biliary atresia because it is not an effective way of reducing the incidence of postoperative cholangitis, and it may be deleterious to liver function.

The need for paediatric liver transplantation, which in most paediatric series is the remedy for biliary atresia after Kasai's operation has failed, is not sufficiently covered by organ retrieval at the present time. In most cases, survival after liver transplantation in children is approximately 80%. Mortality is still high due to intra-operative complications in most cases. Morbidity is related to vascular complications as well as to different types of infections which occur in nearly all the children. After the initial period, growth in most children returns to normal with normal physical and intellectual development. There remain a number of questions concerning the future of liver transplantation in children. What are the limits for proper indications and contraindications? What is the risk of life-long immunosuppressive treatment? Are there alternative modalities of treatment other orthotopic liver transplantation? It must be admitted that before progress has provided answers to these questions and a better understanding of the aetiology of many congenital or metabolic diseases in children as well as a better means of treatment or prevention, that the need for liver grafts in children will continue to rise as a consequence of its own success. One point must be emphasized, since we are concerned with very young children, care should always be given by specially trained health care providers.

Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

Transplantation of the liver has progressed in recent years and has become universally accepted for numerous indications in end-stage liver diseases, predominantly primary biliary cirrhosis, sclerosing cholangitis, biliary atresia and liver-related metabolic disorders. In fulminant and subfulminant hepatitis, prognosis has been improved considerably by liver transplantation. The debate still persists whether liver transplantation might be indicated in diseases recurring after transplantation, such as HBV cirrhosis. Alcoholic cirrhosis as an indication for transplantation remains still controversial. The risk of tumor recurrence after transplantation for small hepatocellular carcinoma in cirrhosis can be calculated; adjuvant chemotherapy might increase prognosis. Transplantation for other malignant liver tumors seems to be obsolete.

Hepatic calcification was found in an anicteric infant with biliary atresia after hepatic portoenterostomy. When she was 2 years of age, ultrasonography detected an echogenic structure with acoustic shadowing. Computerized tomography located it at the proximal portion of Segment 6 in the right lobe. Although both techniques failed to exhibit dilatation of the peripheral bile ducts, we believe intrahepatic cholelithiasis provides the most likely diagnosis. Although seven cases with biliary atresia were reported to have this complication, all of them were icteric when the diagnosis was confirmed. The patient should be carefully followed up since the succeeding stones may cause jaundice by obstructing the main duct.

Liver transplantation is an accepted and successful mode of treatment for pediatric end-stage liver disease. On the basis of a review of 229 liver transplantations in 185 children, the authors describe the imaging findings of the preoperative evaluation, the uncomplicated transplantation, various postoperative complications, and the suggested percutaneous treatment of some of these complications. The most frequent indications for liver transplantation encountered in this review were biliary atresia (52%), acute fulminant hepatic failure (11%), alpha 1-antitrypsin deficiency (9%), cryptogenic cirrhosis (6%), and chronic active hepatitis (4%). (The remaining 18% were various rare indications, representing < 4% each.) Routine Doppler ultrasound is the modality of choice for the screening of postoperative complications, supplemented with computed tomography, hepatobiliary scintigraphy, and cholangiography or angiography as needed. Familiarity with the normal graft appearance, as influenced by various surgical and technical factors, and knowledge of the underlying condition of the patient and the clinical course of postoperative complications are crucial for a correct interpretation of the findings from imaging studies.

In order to evaluate liver function in postoperative biliary atresia (BA) patients, the indocyanine green (ICG) clearance test was performed. Nineteen patients, ranging in age from 2 to 9 years, were classified into three groups. Group I were those who had no jaundice throughout the postoperative period (n = 9), Group II were those who had recurrent or intermittent jaundice (n = 7), and Group III were those who had persistent jaundice after hepatic portojejunostomy (n = 3). Forty-four volunteers of comparative age and sex served as controls to establish a normal range of ICG-K values in infants and children. The normal minimal ICG-K value in those 2-9 years of age was defined as 0.19. ICG-K values in BA patients were 0.262 +/- 0.073 (Group I), 0.150 +/- 0.060 (Group II), and 0.054 +/- 0.011 (Group III). All nine patients with ICG-K below the normal level had esophageal varices, and seven of nine had a history of gastrointestinal hemorrhage. Two patients with ICG-K values within the normal range had esophageal varices, and none had a history of gastrointestinal hemorrhage. Five of nine patients with ICG-K values below normal had low serum albumin levels, and all had low prealbumin levels. Of those with ICG-K within the normal range, none had low serum albumin or prealbumin levels. On the other hand, serum bilirubin and other liver function tests did not accurately reflect clinical findings. In conclusion, the ICG test using the ICG-K value was confirmed to be a reliable indicator of postoperative liver function in BA patients.

The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506.

Liver function tests (LFTs) are an essential assessment parameter when evaluating a child's liver function. This article reviews the interpretation of LFTs and summarizes physioanatomic considerations.

Indications for and results of orthotopic liver transplantation (OLT) were modified over the past ten years by new immunosuppressive agents, earlier timing of transplantation and better knowledge of potential complications. In 1990, OLT appears justified in the treatment of all liver disease threatening life, in the absence of contraindications and other possible treatments. Between July 1987 and December 1990, 21 patients were transplanted at the Geneva University Hospital. Three children received part of an adult liver (two or three segments), using the reduced-size liver transplantation technique. Four OLTs had to be performed in an emergency situation. Two patients died within six months of transplantation, one after 7.5 months, and the last patient died after one year from cancer recurrence. 17 patients are presently alive (81%) at 4 to 39 months (median 14 months) following OLT. More than the mere survival, however, the quality of life regained after transplantation prompts us to consider transplantation early in the progress of the disease.