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Aims: Cellular senescence plays a role in tumour suppression and in the pathogenesis of various non-neoplastic diseases, including primary biliary cholangitis and other adult cholangiopathies. Less is known about the role of cellular senescence in cholangiopathies in children. With that in mind, we examined the expression of senescence-associated cell cycle regulators in biliary atresia, the most common form of paediatric obliterative cholangiopathy., Methods and Results: The expression of senescence-associated cell cycle regulators (p16 Ink4a and p21 WAF ) and a ductular reaction related marker (neural cell adhesion molecule: NCAM) was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia [n = 80; including 23 samples at the time of the Kasai procedure (KP) and 63 obtained from the explanted liver (LT) (six cases with samples at both surgical stages of disease)] and from appropriate controls (n = 17). The degree of ductular reaction and cholestasis was significantly more extensive in LT than KP (P < 0.01). The expression of p16 1/Cip1 ) and a ductular reaction related marker (neural cell adhesion molecule: NCAM) was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia [n = 80; including 23 samples at the time of the Kasai procedure (KP) and 63 obtained from the explanted liver (LT) (six cases with samples at both surgical stages of disease)] and from appropriate controls (n = 17). The degree of ductular reaction and cholestasis was significantly more extensive in LT than KP (P < 0.01). The expression of p16 INK 4a and NCAM was significantly more extensive in bile ducts and bile ductules in ductular reaction in both KP and LT compared to controls and in LT compared to KP (P < 0.05). The expression of p21 WAF 1/Cip1 was significantly more extensive in bile ducts and bile ductules in KP compared to both LT and controls (P < 0.01)., Conclusions: Cellular senescence may play a role in the progression of bile duct loss in biliary atresia in a manner similar to that of adult cholangiopathies., (© 2018 John Wiley & Sons Ltd.)

Biliary atresia (BA) accounts for most cases of pathologic infantile jaundice, which may lead to cirrhosis and eventually necessitate liver transplantation (LT). A cardinal histologic feature of BA is ductular reaction (DR), reflecting activation of the regenerative compartment in liver. We examined the immunohistochemical attributes of the progenitor cell population and its immediate descendants in BA patients undergoing Kasai procedure (KP) or LT. The BA cases were divided into those undergoing KP (n = 24) and those undergoing LT (n = 64). Immunohistochemistry for CD56, CK7, and CK19 was performed. Patients with BA (both KP and LT groups) had more DR than controls (scores 2.4, 2.2, and 0.1, respectively; P < .001), but the degree of DR did not differ between BA patients undergoing KP compared to LT. There was significantly more CD56 staining in DR in LT (2.5) versus KP samples (1.3; P < .001), with a trend toward the same pattern in hepatocyte progenitor cells in these samples (0.6 versus 0.2; P = .05). In intermediate hepatocytes, CK7 staining was higher in LT versus KP samples (1.7 versus 0.3; P < .001). No differences in CK19 staining were noted in the cell types in different BA groups. Immunohistochemistry suggests that the regenerative compartment is expanded in patients undergoing LT for BA, compared to patients with an earlier stage of disease undergoing KP. These observations support the notion that there is more active regeneration in livers with advanced-stage BA and highlight the immunophenotypic heterogeneity of progenitor cells in different phases of the disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Biliary atresia-induced cholestasis increases hepatic oxidative stress with eventual progression to cirrhosis and liver failure. Omega-3 fatty acids play a possible role in the regulation of oxidative stress and the improvement of cholestasis., Aim: The goal of the present study is to investigate the role of dietary supplementation of fish omega-3 fatty acids in the reduction of hepatocellular damage by using a rat common bile duct ligation model., Methods: Sprague-Dawley rats received either sham or bile duct ligation (BDL) and were divided into four study groups: Sham+saline (Sham+sal) group, Sham+Fish oil (Sham+FO) group, BDL+saline (BDL+sal) group, and BDL+Fish oil (BDL+FO) group. Rats from each group were assigned to receive, besides regular chow, once daily with either normal saline or fish omega-3 fatty acids (0.4 % of its own body weight) via gavage for 10 days. Samples of blood, liver tissue homogenates, and histological studies from different groups were analyzed at the end of the study., Results: Rats from BDL+FO had significantly impaired liver function as compared to other study groups (p < 0.05 is of significant difference). Ishak scores and the TGF-b1 contents were significantly higher in rats that received BDL+FO, p < 0.05. Contrary to TGF-b1 liver content, rats from the BDL+FO group had the lowest glutathione levels among the study groups, p < 0.05., Conclusions: Fish omega-3 fatty acids supplementation, albeit increased tissue content of DHA, tended to increase liver fibrosis in BDL rats, decrease liver glutathione level, and compromise hepatic function; fish oil supplementation to subjects with biliary atresia might be of potential hazard and should be used with caution.

Objectives: Oxidative stress is known to be involved in the pathogenesis of biliary atresia (BA), but the mechanism has yet to be elucidated. We studied 8-hydroxydeoxyguanosine (8-OHdG) and mitochondrial copy number as potential markers for oxidative stress in BA., Methods: Hepatic immunoreactive 8-OHdG expression was investigated during the early stage of BA when the patients received Kasai portoenterostomy (KP), during the late stage when the patients received liver transplantation (LT), in patients with choledochal cyst as disease control, and in patients with histologically normal liver as normal control. Apoptosis of liver cells was examined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end-labeling stain. The mitochondrial DNA copy number was measured by real-time polymerase chain reaction., Results: The number of hepatocytes positive for immunoreactive 8-OHdG was significantly increased in KP (65% +/- 18%) compared with LT (30% +/- 32%; P = 0.029) and choledochal cyst (25% +/- 20%; P = 0.037). The 8-OHdG labeling index was significantly correlated with the grade of chronic hepatitis activity (Spearman r = 0.495; P = 0.037). The hepatocyte terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end-labeling index in KP (15% +/- 4%) was significantly higher than that in LT (5% +/- 2%; P = 0.018) and in choledochal cyst (3% +/- 2%; P = 0.010). Mitochondrial copy number was significantly less in KP than in LT (7.33 +/- 0.75 vs 8.91 +/- 1.32; P = 0.045) and in normal control (7.33 +/- 0.75 vs 9.20 +/- 1.20; P = 0.021)., Conclusions: The early stage of BA is associated with stronger inflammatory reaction, augmented oxidative DNA, and mitochondrial DNA damage as manifested by higher immunoreactive 8-OHdG and apoptotic activities and by a decrease in mitochondrial copy number.

Abstract: The thymus gland possesses the ability to regrow in children leading to a newly developed anterior mediastinal mass. This condition may represent a rebound phenomenon during recovery from a stressful event such as post‐chemotherapy and hence was described as RTH. RTH after LT has not been well documented. We are reporting an infant with BA who underwent LT and presented with a symptomless anterior mediastinal mass, detected on follow‐up imaging 6 months thereafter. Surgical partial excision was performed to rule out other differential diagnoses of a solid mass in the anterior mediastinum of an infant particularly lymphoma—that may arise as post‐transplant lymphoproliferative disorder—and teratoma, as well as the other aggressive lesions such as thymoma and thymic carcinoma. The final pathological analysis revealed true thymic hyperplasia, consistent with RTH. The diagnosis of RTH should be considered for a child presenting by anterior mediastinal mass after LT. [ABSTRACT FROM AUTHOR]