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Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P =.0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. Pre-transplant TPN was safe and effective for patients with end-stage BA. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to elucidate the difficulties faced by adult native liver survivors with biliary atresia (BA) in Japan. Methods: A single-center, retrospective, observational study of 57 adult patients with BA was conducted. The clinical course of BA was compared between native liver survivors and non-survivors who reached adulthood. Indications and outcomes of liver transplantation (LT) among non-survivors were assessed. Results: A significantly larger portion of non-survivors (n = 10) met the criteria for LT (p < 0.001) and received treatment for portal hypertension after reaching 20 years of age (p < 0.01) compared with the survivors. Causes of death included liver cirrhosis (n = 8), graft failure of living donor liver transplantation (LDLT) (n = 1), and hepatocarcinoma (n = 1). Two of the non-survivors who died of liver cirrhosis had no indication for LT because of alcohol dependence and uncontrolled infection. An appropriate donor candidate could not be found for the five patients who opted for LDLT. All six patients waitlisted for deceased donor liver transplantation (DDLT) died after a median waiting period of 17 months. Conclusion: Adult BA patients in Japan have limited options for LT, mainly owing to low donor candidate availability for LDLT and a low prevalence of DDLT. [ABSTRACT FROM AUTHOR]

Background: Esophagogastric varices (EGVs) may develop as a result of portal hypertension in children with biliary atresia (BA). Although endoscopic injection sclerotherapy (EIS) with ethanolamine oleate (EO) is reported useful for children, risk factors associated with the presence of high‐risk EGVs after treatment remain unknown. Methods: The subjects were BA patients under 15 years of age who underwent EO‐EIS. We retrospectively reviewed a total of 28 treatment sessions of EGVs with red signs and those larger than F2, which were considered to be at high risk of bleeding. Survival analysis was performed for the presence of high‐risk EGVs at the time of follow‐up endoscopy as the occurrence of an event. Results: Univariate analysis showed a significantly increased risk of the presence of high‐risk EGVs post‐EO‐EIS in patients with increased liver stiffness (LS) and Mac‐2 binding protein glycan isomer (M2BPGi), with hazard ratios of 1.48 and 1.15, respectively. The median presence‐free period was significantly shorter in the LS ≥ 2.8 m/s patients than in those with LS <2.8 m/s (189 vs. 266 days). Similarly, the median presence‐free period was significantly shorter in patients with M2BPGi ≥ 4.0 than in those with M2BPGi < 4.0 (182 vs. 203 days). The results of multivariate analysis revealed that the risk of the presence of high‐risk EGVs was significantly higher only in the high‐LS group, with a hazard ratio of 2.76. Conclusions: Increased LS is associated with risk of the presence of high‐risk EGVs following EO‐EIS in children with BA. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is among the commonest indications for liver transplantation (LT) in children. We examined whether serum matrix metalloproteinase‐7 (MMP‐7) is useful for diagnosis of BA in Japanese infants, and whether serum MMP‐7 concentrations before and after Kasai portoenterostomy (KP) predicted LT within a year. Methods: Subjects under 6 months old at eight pediatric centers in Japan were enrolled retrospectively, including patients with cholestasis and normal controls (NC) without liver disease. Patients with cholestasis were divided into groups representing BA versus cholestasis from other causes (non‐BA). Serum samples were collected from patients with BA at diagnosis and 1 and 4 weeks after KP, as well as from non‐BA and NC. Results: Serum MMP‐7 concentrations were significantly higher in BA at diagnosis (median, 89.1 ng/ml) than in non‐BA (11.0; p < 0.001) or NC (10.3; p < 0.001). Receiver operating characteristic (ROC) analysis of MMP‐7 for BA versus non‐BA yielded an area under the ROC curve of 0.99 (95% confidence interval, 0.96–1.00). An optimal cut‐off value of 18.6 ng/ml for serum MMP‐7 in diagnosing BA demonstrated sensitivity and specificity of 100% and 90%, respectively. Serum MMP‐7 before and 1 week and 4 weeks after KP did not differ significantly between BA requiring only KP and BA requiring LT after KP. Conclusion: Serum MMP‐7 is a useful marker for diagnosis of BA in Japanese infants, but it could not predict LT within a year. [ABSTRACT FROM AUTHOR]

Purpose: Kasai portoenterostomy (KP) is the primary procedure for biliary atresia (BA). However, due to reports of poor outcomes of KP, primary liver transplantation (LT) is preferred in selected cases. In Japan, primary LT is limited with no study reports details, particularly regarding the indications. We conducted the first nationwide survey to assess the status of primary LT in Japan.Methods: Questionnaires were sent to institutions where procedures other than KP were performed as the initial procedure for BA and registered to the Japan Biliary Atresia Registry. Parameters related to procedure selection were analyzed.Results: Of 2895 patients registered (1989-2013), primary LT (n = 15) or exploratory laparotomy (EL) followed by LT (n = 9) without KP was performed in 24 cases (0.8%). The main reason for primary LT was late diagnosis, and for EL followed by LT, lack of fibrous tissue at the porta hepatis (ο-type). The prognoses of LT without KP was good.Conclusion: Non-KP initial procedures were limited. Clear criteria regarding the timing of diagnosis or patient condition could not be determined. Reasons for not initially selecting KP varied, but late diagnosis was predominant. Further study is needed to create guidelines for the initial treatment of BA patients. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular injury including multinuclear changes are common histological features in biliary atresia (BA), as well as in neonatal hepatitis. To date, however, no reports have examined how those findings correlate with the prognosis of BA. We clarified the clinical implications of hepatitis‐related changes in BA on histological analysis. Methods: We retrospectively reviewed 34 cases of BA treated over the past 30 years at Ibaraki Children's Hospital. Liver biopsy specimens during Kasai procedures were evaluated for hepatocyte multinuclear change, ballooning, and acidophilic body, hereby defined as hepatitis‐like findings (HLF). Each finding was semi‐quantitatively scored as 0–2, and their sum was defined as the HLF score, ranging from 0 to 6. We examined the correlation between HLF score and total bilirubin (T‐Bil), direct bilirubin (D‐Bil), and other liver function test results at the Kasai procedure, as well as 1 week, and 1, 3, and 6 months after the Kasai procedure. Subsequently, HLF score was compared between native liver survivors (NLS; n = 16) and non‐NLS (n = 18) for long‐term analyses. Results: Hepatitis‐like findings score except for aspartate aminotransferase (AST), had no correlation with the preoperative data. HLF score was positively correlated, however, with T‐Bil, D‐Bil, and AST at 1 week and 1 month after the Kasai procedure (1 week: P = 0.009, 0.023, and 0.019; 1 month: 0.022, 0.019, and 0.013, respectively). HLF score was not significantly different between the NLS and non‐NLS groups. Conclusion: Higher HLF score at Kasai procedure is an indicator of poor liver function at short‐term follow up. [ABSTRACT FROM AUTHOR]

Abstract: Background: Health‐related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant‐specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT). Methods: A cross‐sectional survey using anonymous questionnaires was completed between April and July 2015. Patient medical records were accessed. The Japanese version of Pediatric Quality of Life InventoryTM Generic Core Scales and Transplant Modules (child self‐report and parent proxy‐report) was administered. Results: Participants consisted of 75 patients (mean age at survey, 9.6 years) and 74 parents. Japanese patients reported higher generic and transplant‐specific HRQOL (total score) than that reported by US patients with BA after LT (US I; age at survey, 7.2 years) and by US patients after solid organ transplant (US II; age at survey, 11.3 years; LT, 53.8%; effect size, 0.55–0.96). Japanese parents, however, rated their children's generic HRQOL (total score) similar to that rated by the US I and II parents (0.13 and 0.30, respectively) and reported lower transplant‐specific HRQOL (total score) than that reported by US II (0.26). Although the number of types of prescribed drugs was a common factor in HRQOL, most demographic and medical factors (e.g. child's age at survey and consultation frequency) varied with reporter (i.e. patients and parents). Conclusions: The levels and factors of generic and transplant‐specific HRQOL of Japanese pediatric and adolescent patients with BA after LDLT varied with reporter (i.e. patients or parents). [ABSTRACT FROM AUTHOR]

Background So far, there has been no epidemiological study on whether long-term native liver survival ( NLS) in infants with biliary atresia ( BA) is associated with use of a stool color card ( SCC). Methods A case-control study was performed, involving two associations for patients with BA in Japan. Participants were patients with BA who were born and underwent their first open Kasai procedures ( KP) between August 1994 and March 2011, and who were also members of either of two associations for patients with BA in Japan. SCC users were classified as cases and SCC non-users as controls. Results Mean age at the time of the first open KP was 59.7 and 68.2 days in SCC users and non-users, respectively ( P < 0.05). According to Kaplan-Meier analysis, the probability of NLS at 12.5 years was 48.5% and 36.6% in SCC users and non-users ( P < 0.05), respectively. On Cox proportional hazard modeling, not using an SCC was harmful to long-term NLS (hazard ratio, 2.61; 95% CI: 1.20-5.70; P = 0.016), adjusted for sex, age of timing of KP and type of BA. Conclusions Long-term NLS is associated with SCC for early detection, but not associated with age or a threshold of age at KP (<90 days) in patients with BA. [ABSTRACT FROM AUTHOR]

Background: The stool color card has been the primary tool for identifying acholic stools in infants with biliary atresia (BA), in several countries. However, BA stools are not always acholic, as obliteration of the bile duct occurs gradually. This study aims to introduce Baby Poop (Baby unchi in Japanese), a free iPhone application, employing a detection algorithm to capture subtle differences in colors, even with non-acholic BA stools.Methods: The application is designed for use by caregivers of infants aged approximately 2 weeks-1 month. Baseline analysis to determine optimal color parameters predicting BA stools was performed using logistic regression (n = 50). Pattern recognition and machine learning processes were performed using 30 BA and 34 non-BA images. Additional 5 BA and 35 non-BA pictures were used to test accuracy.Results: Hue, saturation, and value (HSV) were the preferred parameter for BA stool identification. A sensitivity and specificity were 100% (95% confidence interval 0.48-1.00 and 0.90-1.00, respectively) even among a collection of visually non-acholic, i.e., pigmented BA stools and relatively pale-colored non-BA stools.Conclusions: Results suggest that an iPhone mobile application integrated with a detection algorithm is an effective and convenient modality for early detection of BA, and potentially for other related diseases. [ABSTRACT FROM AUTHOR]

Background: We assessed postoperative outcome in relation to the level of transection of the biliary remnant at the time of laparoscopic Kasai portoenterostomy (LKP) in biliary atresia (BA) patients.Methods: The subjects for this study were 12 consecutive nonsyndromic type III BA patients who had LKP at our institute between 2009 and 2014. All LKPs were video recorded. Four board-certified pediatric surgeons assessed the level of transection of the biliary remnant and suturing during the anastomosis in each video blindly. A standard protocol was used for postoperative management.Results: The level of transection was assessed as being shallow and suturing techniques as being identical in all. Although all cases achieved jaundice disappearance, 4 required liver transplantation (NNL group) for relapse of jaundice and 8 remain anicteric with native livers after mean follow-up of 4.6 years (NL group). Demographic data (birth weight, weight and age at LKP, duration from onset of symptoms to LKP, size of microbile ducts, and preoperative biochemical markers) were similar for both groups.Conclusions: The level of transection of the biliary remnant and suturing techniques would appear to not directly influence the outcome of LKP. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to describe the following: maternal coping with the prospect of becoming the living-donor liver transplant for their child; the daily lives of school-age children surviving biliary atresia with their native liver; and to explore the relationship between these individuals. Semistructured interviews were conducted with 6 school-age children surviving biliary atresia with their native liver and their mothers. The interviews were conducted from June to August 2014, and a qualitative content analysis was used. Results showed that mothers realized a possible need for transplantation in the future, which contributes to emotional and practical uncertainties. The mothers coexisted with this uncertainty and preferred to use a buffering strategy. In contrast, the children did not consider their illness and future and did not adhere to a therapeutic regimen. It is suggested that living with uncertainty about the health and survival of their children is advantageous for mothers. However, problems related to the psychosocial aspect and child's adherence may occur in the future. In addition, problem-solving coping strategies for mothers and the independence of chronically ill children with liver disease should be promoted. [ABSTRACT FROM AUTHOR]

Purpose: Long-term survivors of biliary atresia (BA) sometimes experience liver dysfunction. We evaluated the prognostic factors for long-term native liver survival (NLS) in BA patients after the Kasai procedure.Methods: This study included 67 patients with jaundice disappearance after the Kasai procedure performed between 1972 and 1995, and NLS for over 10 years. We retrospectively evaluated the clinical parameters, including the type of BA, age at the Kasai procedure, medical conditions, and treatments. The adjusted odds ratios (aOR) were obtained for 20-year NLS using logistic regression analysis.Results: The median age of the patients at the Kasai procedure was 63 days. Of the 67 study patients, 62 patients (92.5 %) had jaundice-free NLS at the age of 20 years, 4 patients died before the age of 20 years from liver failure, and 1 patient underwent living related liver transplantation. The presence of gastro-esophageal varices requiring endoscopic injection sclerotherapy was a significant factor (aOR 33.8; p = 0.0033), while hypersplenism and cholangitis were not identified as significant factors.Conclusions: The existence of symptomatic portal hypertension would influence long-term NLS in BA patients after the Kasai procedure. In such patients, accurate evaluation of hepatic function and adequate treatment for sequelae are needed. [ABSTRACT FROM AUTHOR]

Background: Measurement of urinary sulfated bile acid (USBA) is a non-invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). Methods: We determined the USBA-to-creatinine ratio (USBA/cr) in 1148 infants at 10-40 days after birth. All infants were followed until the 3- to 4-month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. Results: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow-up period. Conclusion: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false-positive rate is decreased by improving the methods for sample collection and urine storage. [ABSTRACT FROM AUTHOR]

Purpose: Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department.Patients and Methods: The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B).Results: Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p < 0.01). Duration of surgery was an independent risk factor (p = 0.05).Conclusion: Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long. [ABSTRACT FROM AUTHOR]

Purpose: The occurrence of thrombocytopenia in the perioperative period after liver transplantation (LT) in patients with portal hypertension is not uncommon. In most cases, thrombocytopenia in the early period after LT recovers with the restoration of the graft hepatic function. In contrast, the recovery of pre-transplant thrombocytopenia differs among patients, and some patients experience persistent thrombocytopenia and splenomegaly even several years after LT.Methods: We retrospectively reviewed the clinical records of 38 liver transplant patients who had at least a 1-year follow-up in our institute. The serial platelet counts and the spleen volumes estimated by the CT scans were obtained before LT and at 1 month, 1 year, and 3 years after LT. In cases with persistent thrombocytopenia (less than 100,000/μl beyond 1 year after LT) and splenomegaly after LT, the associated clinical factors were reviewed.Results: The platelet counts increased and the spleen volumes decreased continuously in most cases after LT. However, six patients (15.8%) were categorized as persistent thrombocytopenia. The spleen volumes of these six patients decreased more slowly after LT, and, in some cases, showed even re-increased volumes. The factors such as the age at LT, GRWR, the existence of hepatopulmonary syndrome, and the existence of biliary complication after LT were associated with persistent thrombocytopenia after LT.Conclusions: The evaluation of the pre-transplant spleen volumes and the platelet counts before LT thus makes it possible to predict the persistent thrombocytopenia after LT. [ABSTRACT FROM AUTHOR]

To re-evaluate the impact of recipient age on the outcome of LDLT for BA in an era in which LDLT is the established treatment for BA in Japan. Thirty-one patients with BA who underwent LDLT were divided into four groups regarding the age at LDLT: infants <1 yr old (group A; n = 14); young children 1 to 6 yr old (group B; n = 8); school children 6 to 15 yr old (group B; n = 5); and adults ≥15 yr old (group D; n = 4). Pre-, peri-, and postoperative factors were compared among the four groups. There was no significant difference in number of the previous laparotomy among the groups. Cholestasis was the dominant indication in group A. PELD score in group B was lower than that in the other groups, and blood loss in group B was significantly less than in groups A and D. Ratio of the graft weight to the recipient’s body weight (GRWR) in group A was significantly higher than in other groups. Duration of operation in group D was lower than in groups A and B, but there was no significant difference in the length of postoperative hospital stay and graft survival. Although the case volume was not big, the age of the recipient did not have any significant impact on the outcome of LDLT in our series. [ABSTRACT FROM AUTHOR]

During the last decade, biliary atresia (BA) has attained more interest and the frequency of BA-related publications has increased continuously. Pediatric hepatologists and pediatric surgeons are very active in improving diagnosis and treatment modalities of BA patients, in order to prolong the survival rate of their native liver. Together with transplant surgeons, the bridging of BA patients to liver transplantation (LTx) becomes optimized and as a consequence of this interdisciplinary approach, the overall survival of babies with BA has already reached 90%. Furthermore, basic research into the still unknown origin of BA has advanced, and numerous scientific programs have already linked together. The overriding interest is to discover at least BA's etiology and to turn the treatment of BA patients from a symptomatic to a causative approach. Interdisciplinary and international programs are mandatory and already existing initiatives in Europe, the United States and Japan are going to coordinate their registries, clinical trials and basic research studies for the benefit of the patients and solve the riddle of BA. [ABSTRACT FROM AUTHOR]

Summary: 1. Biliary atresia (BA), as a common disease in Japan, and cystic fibrosis (CF), as an extremely uncommon disease in Japan, were selected to assess the clinical significance of measurement of energy expenditure (EE). 2. Energy expenditure was significantly higher in children with BA than in normal children. 3. Measurement of EE in BA lead to clues to resolving its mechanism by novel assessment of interleukin‐6 and leptin. 4. Energy expenditure in children with CF is also higher, but this has been addressed by nutritional intervention with additional calories. 5. Individualization of EE measurement is necessary in the analysis of pathological mechanisms and nutritional management of patients with both common and uncommon diseases. [ABSTRACT FROM AUTHOR]

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs. [ABSTRACT FROM AUTHOR]

The cancer burden in Asia has been focused not only in developed countries but also in Low and Middle-Income Countries. However, there are few countries equipped with reliable data for cancer control. In Japan, cancer became reportable under the Act on Promotion of Cancer Registry, unifying databases, and grasping all deaths, which guarantee complete cancer incidence database in theory. In Korea and Taiwan, the development of cancer statistics at the national level has been completed ahead of Japan. For the analysis of rare cancer data, case finding, classification and aggregation of information in accordance with international standards are essential. As part of the RARECAREnet project promoted by the National Institute of Tumour in Milan, Italy, this program was officially launched in Asia, and was able to coordinate from the proposal, definition, and protocol edition phase. As it is difficult to submit data to international research these days, we have conducted analysis in each country based on SEER* Stat. ata quality in the three Asian countries were as high as EU. Based on the revised RARECARE definition (crude incidence <6/100,000/year in tier-1), the incidence of all rare cancers was 93.9 in Japan, 106.1 in Korea and 103.5 in Taiwan and 67.8 in EU corresponding to 14%, 24.0%, 24% and 11% of all cancer diagnoses. Among rare cancer families, epithelial tumours of nasopharynx, oropharynx and oral cavity and lips were not rare in Taiwan. Epithelial tumours of oral cavity and lip was not rare in Japan, neither. Epithelial tumours of gallbladder and extra hepatic biliary tract was not rare in Japan and Korea. Thyroid cancer was not rare in all three Asian countries. Most of the continental gaps found in the current study were due to well known risk factors, and we conclude that EU based RARECARE rarity threshold fits well to cancer incidence in East Asia. [ABSTRACT FROM AUTHOR]