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Dehua Wang, Darren Marshall, Gruschen Veldtman, Anita Gupta, Andrew T Trout, Juan Villafane, Kevin Bove
Hepatic dysfunction, including development of hepatocellular carcinoma and other liver lesions has been increasingly reported following Fontan procedure for congenital heart disease. We report a unique case of intrahepatic cholangiocarcinoma 28 years after a Fontan procedure in a 31year old female with heterotaxy syndrome. The subcapsular mass-forming tumor was composed of poorly differentiated tumor cells arranged in small vague glandular or slit-lumen nests, and focally fused or anastomosing large trabecular patterns within the prominent fibrotic stroma...
March 15, 2018: Pathology, Research and Practice
Bilon Khambu, Nazmul Huda, Xiaoyun Chen, Daniel J Antoine, Yong Li, Guoli Dai, Ulrike A Köhler, Wei-Xing Zong, Satoshi Waguri, Sabine Werner, Tim D Oury, Zheng Dong, Xiao-Ming Yin
Autophagy is important for liver homeostasis and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here we reveal the role of highmobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPC) implicated in liver repair and regeneration. DR caused by hepatic toxic diets (DDC or CDE) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios...
March 20, 2018: Journal of Clinical Investigation
Céline Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
March 20, 2018: Journal of Clinical Investigation
M Garrido, C Escobar, C Zamora, C Rejas, J Varas, C Córdova, C Papuzinski, M Párraga, S San Martín, S Montedonico
Purpose: Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods: Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks...
2018: Stem Cells International
Hajime Okada, Minami Yamada, Kenji Kamimoto, Cindy Yuet-Yin Kok, Kota Kaneko, Masatsugu Ema, Atsushi Miyajima, Tohru Itoh
Under various conditions of liver injury, the intrahepatic biliary epithelium undergoes dynamic tissue expansion and remodeling, a process known as ductular reaction. Mouse models defective in inducing such a tissue-remodeling process are more susceptible to liver injury, suggesting a crucial role of this process in liver regeneration. However, the molecular mechanisms regulating the biliary epithelial cell (BEC) dynamics in the ductular reaction remain largely unclear. Here, we demonstrate that the transcription factor Krüppel-like factor 5 (Klf5) is highly enriched in mouse liver BECs and plays a key role in regulating the ductular reaction, specifically under cholestatic injury conditions...
March 9, 2018: Journal of Biological Chemistry
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
Shotaro Nakagun, Akira Shiozaki, Mari Ochiai, Ayaka Matsuda, Yuko Tajima, Takashi Matsuishi, Kenichi Watanabe, Noriyuki Horiuchi, Yoshiyasu Kobayashi
Beaked whales are among the least known group of cetaceans, and information regarding their pathology and parasitology is especially scarce. We describe a case of significant parasitism by a trematode found in the liver of an adult male Hubbs' beaked whale Mesoplodon carlhubbsi that stranded in Hokkaido, Japan. Post-mortem examinations revealed a localised area of discolouration restricted to the hilar region of the left hepatic lobe, where spindle-shaped trematodes occupied the dilated and hypertrophic bile ducts...
March 5, 2018: Diseases of Aquatic Organisms
Adrien Guillot, Imène Gasmi, Arthur Brouillet, Yeni Ait-Ahmed, Julien Calderaro, Isaac Ruiz, Bin Gao, Sophie Lotersztajn, Jean-Michel Pawlotsky, Fouad Lafdil
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other...
March 2018: Hepatology Communications
Aude Merdrignac, Gaëlle Angenard, Coralie Allain, Kilian Petitjean, Damien Bergeat, Pascale Bellaud, Allain Fautrel, Bruno Turlin, Bruno Clément, Steven Dooley, Laurent Sulpice, Karim Boudjema, Cédric Coulouarn
Intrahepatic cholangiocarcinoma (iCCA) is a deadly liver primary cancer associated with poor prognosis and limited therapeutic opportunities. Active transforming growth factor beta (TGFβ) signaling is a hallmark of the iCCA microenvironment. However, the impact of TGFβ on the transcriptome of iCCA tumor cells has been poorly investigated. Here, we have identified a specific TGFβ signature of genes commonly deregulated in iCCA cell lines, namely HuCCT1 and Huh28. Novel coding and noncoding TGFβ targets were identified, including a TGFβ-induced long noncoding RNA (TLINC), formerly known as cancer susceptibility candidate 15 (CASC15)...
March 2018: Hepatology Communications
Margarita N German, Kristina A Matkowskyj, Robert J Hoffman, Parul D Agarwal
While the incidence of syphilis has been persistently on the rise in the United States, hepatitis as a complication of early syphilis is relatively uncommon. We present a case of a 51-year-old homosexual, HIV-positive male who presented with acute cholestatic hepatitis with a predominantly elevated alkaline phosphatase. After lab studies and imaging were unrevealing, a liver biopsy was performed that showed expanded portal tracts with a predominantly lymphoplasmacytic infiltrate and prominent bile ductular proliferation with periductal neutrophils...
March 2, 2018: Human Pathology
Jaya Joshi, Sonalee Shah, Deepak Agarwal, Ankit Khasgiwal
Benign lymphoepithelial cyst (BLC), also known as branchial cyst, is an infrequent lesion usually occurs in the parotid gland or the lateral cervical area including lymph nodes. It occurs due to the process of lymphocyte-induced cystic ductular dilatation and is always diagnosed postoperatively by histopathological examination (HPE). These dysontogenetic lesions are usually found in the lateral neck but can also be located in the salivary glands, mostly in the parotids. A 35-year-old male reported to Government Dental College, Indore, before 3 years, with a soft, nontender, gradually increasing, compressible diffuse swelling involving the left parotid gland for the last 9-10 months of size 3...
January 2018: Journal of Oral and Maxillofacial Pathology: JOMFP
Cinthya Santos Cirqueira, Aloisio Sousa Felipe-Silva, Alda Wakamatsu, Lidiane Vieira Marins, Eziel Cavalcanti Rocha, Evandro Sobroza de Mello, Venâncio Avancini Ferreira Alves
Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays...
February 20, 2018: Pathology Oncology Research: POR
Sarah Hassan, Soheir S Mansy, Sahar A Tabak, Ahmed S AbdelFattah, Ahmed M Abdel-Aziz, Olfat Hamam, Mohammed I Seleem, Amr Abdelaal
Early detection of hepatocellular carcinoma (HCC) is crucial for successful therapy. The present work examined the value of ultrastructural morphometric image analysis of hepatocyte nuclei in patients with chronic hepatitis C virus (HCV) versus HCC cases with chronic HCV and the corresponding surgical tumor-free safe margins (TFMs), to highlight any early predictive signs of neoplastic cellular transformation. This work also performed an immunohistochemical assessment of cytokeratin 19 (CK19) and Ki-67-positive cells to visualize any associated proliferative activity in the examined groups...
February 9, 2018: Ultrastructural Pathology
Umberto Maggi, Giorgio Farris, Alessandra Carnevali, Irene Borzani, Paola Clerici, Massimo Agosti, Giorgio Rossi, Ernesto Leva
BACKGROUND: Double gallbladder is a rare biliary anomaly. Perinatal diagnosis of the disorder has been reported in only 6 cases, and in 5 of them the diagnosis was based on ultrasound imaging only. However, the ultrasound technique alone does not provide a sufficiently precise description of cystic ducts and biliary anatomy, an information that is crucial for a correct classification and for a possible future surgery. CASE PRESENTATION: At 21 weeks of gestational age of an uneventful pregnancy in a 38 year old primipara mother, a routine ultrasound screening detected a biliary anomaly in the fetus suggestive of a double gallbladder...
February 7, 2018: BMC Pediatrics
Usama F Shaalan, Noha L Ibrahim, Nermine A Ehsan, Mervat M Sultan, Ghada M Naser, Mohamed O Abd El-Fatah
Biliary atresia (BA) is a necroinflammatory occlusive cholangiopathy that affects infants. Genetic and environmental factors has been proposed for its occurrence. The objectives of this study was to investigate the protein expression of 2 important genes regulating ductal plate remodeling, hepatocyte nuclear factor 1-beta (Hnf1β) and the fork head box protein A2 (FoxA2) in liver tissue from patients with BA and to compare their expression with other causes of neonatal cholestasis (NC). This retrospective study included 60 pediatric patients, 30 with BA and 30 with NC...
February 5, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Zhen-Wei Peng, Sonja Rothweiler, Guangyan Wei, Naoki Ikenaga, Susan B Liu, Deanna Y Sverdlov, Kahini A Vaid, Maria Serena Longhi, Ming Kuang, Simon C Robson, Yury V Popov
The pathogenesis of primary sclerosing cholangitis (PSC) and the mechanistic link to inflammatory bowel disease remain ill-defined. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1)/clusters of differentiation (CD) 39, the dominant purinergic ecto-enzyme, modulates intestinal inflammation. Here, we have explored the role of CD39 in biliary injury and fibrosis. The impact of CD39 deletion on disease severity was studied in multidrug resistance protein 2 (Mdr2)-/- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of sclerosing cholangitis and biliary fibrosis...
November 2017: Hepatology Communications
Motoko Sasaki, Fang-Ying Kuo, Chao-Cheng Huang, Paul E Swanson, Chao-Long Chen, Jiin-Haur Chuang, Matthew M Yeh
AIMS: Cellular senescence plays a role in tumor 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 pediatric obliterative cholangiopathy. METHODS AND RESULTS: The expression of s senescence-associated cell cycle regulators (p16Ink4a and p21WAF1/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 Kasai-procedure (KP) and 63 obtained from the explanted liver (LT) [6 cases with samples at both surgical stages of disease]) and from appropriate controls (n=17)...
February 2, 2018: Histopathology
Kun Jiang, Sameer Al-Diffhala, Barbara A Centeno
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Jennifer Bailey, Wasim Dar, Kishore Polireddy, Qingzheng Chen, Moises I Nevah Rubin, Amelia Sybenga, Sharon DeMorrow, Fanyin Meng, Lindsey Stockton, Gianfranco Alpini, Heather Francis
Administration of a high-fat diet (HFD) coupled with sugar, mimicking a Western diet, causes fatty liver disease in mice. Histamine induces biliary proliferation and fibrosis, and regulates leptin signaling. Wild-type (WT) and l-histidine decarboxylase (Hdc-/-) mice were fed a control diet or a HFD coupled with a high fructose corn syrup equivalent. H&E and Oil Red O staining were performed to determine steatosis. Intrahepatic biliary mass and cholangiocyte proliferation were evaluated by immunohistochemistry...
December 14, 2017: American Journal of Pathology
Guido Carpino, Vincenzo Cardinale, Trine Folseraas, Diletta Overi, Annarosa Floreani, Antonio Franchitto, Paolo Onori, Nora Cazzagon, Pasquale Bartolomeo Berloco, Tom Hemming Karlsen, Domenico Alvaro, Eugenio Gaudio
Primary sclerosing cholangitis and primary biliary cholangitis are human primary cholangiopathies; these diseases are characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction as the results of hepatic progenitor cell activation. The aims of this study were to evaluate differences in progenitor cell niche activation between these two human cholangiopathies. Human liver tissue was obtained from normal liver donors (n=5), primary sclerosing (n=20), and primary biliary cholangitis (n=20)...
December 14, 2017: American Journal of Pathology
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