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Background: Lymphatic vessels (LVs) play a crucial role in immune reactions by serving as the principal conduits for immune cells. However, to date, no study has analyzed the morphological changes in the LVs of patients with biliary atresia (BA). In this study, we aimed to determine the morphological changes in the LVs irrigating the liver in patients with BA, elucidate their correlations with the morphology of the portal vein (PV) branches, and discuss their etiopathogenetic significance., Methods: Morphometric analyses of liver biopsy specimens from patients treated between 1986 and 2016 were performed. The parameters measured were as follows: the whole liver area of the specimen, fibrotic area, number of LVs, LVs without patent lumen (designated as Ly0) and PV branches, and diameters of the LVs with patent lumen and the PVs., Results: The numbers of LVs, Ly0, and PV branches per unit area of the whole liver specimen were significantly higher in patients with BA than in control participants with liver disease and those with normal livers. However, no correlation was observed between the fibrotic area and the average diameter of LVs or PVs, and between the fibrotic area and the number of LVs or PV branches. Furthermore, no correlation was observed between the total number of LVs and the number of PV branches., Conclusions: The present study showed a significant increase in the number of total LVs and Ly0, characterized by a high Ly0 to total LVs ratio, suggesting that lymphangiogenesis occurs in the liver of patients with BA., (© 2024. The Author(s).)

Purpose: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE)., Methods: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve., Results: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75)., Conclusions: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up., Level of Evidence: Level III., (© 2024. The Author(s).)

Purpose: Frequent post-operative cholangitis in biliary atresia (BA) affects the long-term native liver survival. This study assessed the characteristics of early cholangitis and their influence on the prognosis., Methods: Forty-three patients with BA who underwent surgery between 2000 and 2020 were analyzed for routine inflammatory markers. Early cholangitis characteristics were compared between native liver survivor (NLS) and living donor liver transplant (LDLT) patients., Results: Among the 43 patients, 30 (69.8%) experienced 130 episodes of cholangitis. In the area under the receiver operating characteristics curve (AUROC) analysis, the cutoff value of the total cholangitis episodes was 3, with an area under the AUROC curve of 0.695 (95% confidence interval 0.522-0.868). Before 3 years old, 113 episodes (86.9%) of cholangitis were observed. The white blood cell, C-reactive protein, and alanine aminotransferase values at cholangitis onset did not markedly differ between the LDLT and NLS groups. Conversely, the neutrophil-to-lymphocyte ratio in the NLS group was significantly lower than in the LDLT group (0.85 vs. 1.63, p < 0.001)., Conclusions: Cholangitis in the NLS group was lymphocyte-dominant and atypical in its pathogenesis. Lymphocyte-dominant cholangitis is non-suppurative, and future research should clarify its pathogenesis to improve the treatment and prognosis of BA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT)., Methods: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed., Results: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable., Conclusions: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Various prognostic predictors for biliary atresia (BA) have been identified. This study aimed to evaluate the serial changes in the preoperative and postoperative ubiquitous inflammatory biomarkers and their relationship with the outcomes in patients with BA., Patients and Methods: Forty-three BA patients were retrospectively reviewed to investigate serial levels of ubiquitous inflammatory biomarkers, including C-reactive protein (CRP) and lymphocyte ratio, and outcomes. The patients with BA were divided based on their outcomes into two prognostic groups: the native liver survivor group (n = 30) and the survivors with living-donor liver transplant group (n = 13)., Results: The area under the receiver operating characteristic (ROC) curve analysis showed that a preoperative lymphocyte ratio of < 61% and CRP value > 0.1 mg/dl predicted a poor outcome. In the ROC curve analysis, the timing of reaching the cut-off value of CRP after Kasai portoenterostomy was postoperative day (POD) 57. The third postoperative week, which was the timing of the discontinuation of steroid therapy, was the branchpoint of inflammatory markers between the two prognostic groups., Conclusion: The POD 57 CRP level predicts the surgical outcome of Kasai portoenterostomy. The postoperative anti-inflammatory management of BA can be monitored by the ubiquitous inflammatory biomarkers CRP and the preoperative lymphocyte ratio., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biliary atresia (BA) is an inflammatory disease of the biliary system in newborns and infants. The etiology is largely unknown. Approximately half of BA patients require liver transplantation by 20 years of age, even after surgical correction due to progressive fibrosis of the liver. Regarding the disease mechanism, there is circumstantial evidence to support the hypothesis of graft-versus-host disease because of the existence of maternal cells in the liver (maternal microchimerism, MMC), histopathological similarity of the liver and an intense maternal response to the BA patient with mixed lymphocyte culture. Immune dysregulation with decreased Treg and increased Th1 and Th17 cells are the pathogenic features of BA, which are homologous to the pathogenic features of GvHD. Further elucidation of the etiopathogenetic mechanism of BA is warranted for development of new therapeutic strategies for native liver survival., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim of the Study: We previously showed an increased number of smaller portal vein (PV) branches in the portal areas of liver biopsy specimens of biliary atresia (BA) patients. We evaluated the correlation between this histopathological feature and the prognosis., Patients and Methods: Twenty-five consecutive patients with BA encountered between 2000 and 2012 were classified into three prognostic groups based on their postoperative outcomes: Excellent (n = 11) for native-liver survivors with a normal liver function, Good (n = 6) for native-liver survivors with liver dysfunction, and Poor (n = 8) for survivors after liver transplant or on a waiting list. Data from morphometrical analyses, including the fibrotic portal area, numbers of PVs, diameter and total area of PV branches, were statistically compared among the three groups., Main Results: The number of PV branches per unit area of the whole-liver specimen in the poor prognostic group was significantly lower than that in the excellent group (3.1 ± 0.6 vs. 5.2 ± 2.0/mm 2 , p = 0.03). There were no significant differences in the other parameters., Conclusions: This is the first report on the relationships between morphometrically analyzed PV branches and the postoperative course in BA patients. The portal venous system is involved as the primary lesion in BA.

Purpose: Portal hypertension in patients with biliary atresia (BA) is generally thought to result from portal vein (PV) narrowing secondary to hepatic fibrosis. To test the hypothesis, we morphometrically analyzed the PVs and hepatic arteries (HAs)., Methods: Morphometrical analyses of 25 BA and 26 non-BA liver biopsy specimens from patients treated from 2000 to 2014. The total specimen area, the fibrotic portal area, vessel diameter and medial thickness of the HAs were measured., Results: The PV diameter in BA patients was significantly smaller than that in non-BA patients. In BA, the numbers of normal-sized PVs and capillaries were decreased and increased, respectively. The PV diameter was not significantly correlated with the degree of fibrosis. We newly found that medial hypertrophy and the HA diameter increased with the number of endothelial cells in BA. The PV diameter was not significantly correlated with the medial thickness and was positively correlated with the HA diameter in BA., Conclusions: The narrowing of the PV is unlikely to occur secondarily to liver fibrosis. The medial hypertrophy of the HA is not correlated with the decrease in the PV blood flow. These findings seem to be unique to the primary vascular lesions of BA.

Aim Methods Results Conclusions Inchinkoto (ICKT) is administered to patients with biliary atresia (BA) after surgery. Gardeniae fructus which is contained in ICKT is reported to be associated with idiopathic mesenteric phlebosclerosis (IMP). We investigated the influence of ICKT on calcification of the mesenteric veins suspected of IMP in BA patients.All BA patients with native liver survival who received ICKT after Kasai portoenterostomy were reviewed. All patients underwent abdominal computed tomography (CT) during treatment. Calcification of the mesenteric veins on the most recent CT scan after the initiation of ICKT was assessed.Twenty patients (6 males and 14 females) were enrolled in this study. Of these patients, 17 (85.0%) and 10 (50%) patients had used ICKT for ≥5 years and >10 years, respectively. Calcification of the mesenteric veins was detected in one patient, who was a 14 year old girl. The total dosage of Gardeniae fructus was 21 800 g.The incidence of calcification of the mesenteric veins in BA patients receiving ICKT was low. However, it is necessary to be aware that ICKT containing Gardeniae fructus is associated with the risk of developing calcification of the mesenteric veins suspected of IMP. [ABSTRACT FROM AUTHOR]