Article
Multidisciplinary Sciences
Fotios Sampaziotis, Daniele Muraro, Olivia C. Tysoe, Stephen Sawiak, Timothy E. Beach, Edmund M. Godfrey, Sara S. Upponi, Teresa Brevini, Brandon T. Wesley, Jose Garcia-Bernardo, Krishnaa Mahbubani, Giovanni Canu, Richard Gieseck, Natalie L. Berntsen, Victoria L. Mulcahy, Keziah Crick, Corrina Fear, Sharayne Robinson, Lisa Swift, Laure Gambardella, Johannes Bargehr, Daniel Ortmann, Stephanie E. Brown, Anna Osnato, Michael P. Murphy, Gareth Corbett, William T. H. Gelson, George F. Mells, Peter Humphreys, Susan E. Davies, Irum Amin, Paul Gibbs, Sanjay Sinha, Sarah A. Teichmann, Andrew J. Butler, Teik Choon See, Espen Melum, Christopher J. E. Watson, Kourosh Saeb-Parsy, Ludovic Vallier
Summary: The study demonstrates the potential of cholangiocyte organoids to repair human biliary epithelium, despite the loss of transcriptional diversity during organoid culture, they remain plastic and have regenerative capabilities.
Article
Cell Biology
Ho Taek Oh, Woong Heo, Gi Don Yoo, Kyung Min Kim, Jun-Ha Hwang, Eun Sook Hwang, Jesang Ko, Young-Gyu Ko, Jeong-Ho Hong
Summary: This study found that knockout of ductal TAZ in mice and TAZ in cholangiocyte organoids led to decreased liver fibrosis and decreased expression levels of fibrosis inducers. CD133 stabilized TAZ via Src activation, promoting fibrosis.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sarthak Sahoo, Ashutosh Mishra, Anna Mae Diehl, Mohit Kumar Jolly
Summary: This study identifies the regenerative potential of the liver and the ability of hepatocytes and cholangiocytes to trans-differentiate. Through a gene regulatory network, the study reveals stochastic switching among three different cell states and validates their expression signatures during liver development and regeneration.
Article
Multidisciplinary Sciences
Simona Hankeova, Jakub Salplachta, Noemi Van Hul, Michaela Kavkova, Afshan Iqbal, Tomas Zikmund, Jozef Kaiser, Emma R. Andersson
Summary: The technique described in the study, double resin casting micro-computed tomography (DUCT), involves injecting two different resins into the portal vein and bile duct, followed by tissue fixation, to visualize the three-dimensional structure of the liver. DUCT can be applied to postnatal and adult mouse liver and other tubular networks.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Immunology
Dhiraj Agrawal, Sanjiv Saigal, Shekhar Singh Jadaun, Shweta A. Singh, Shaleen Agrawal, Subhash Gupta
Summary: Paired exchange liver transplantation is an evolving strategy to overcome ABO blood group incompatibility and other barriers in living donor liver transplantation. This study analyzed the experience with liver paired exchange program over the past 9 years and found that with careful attention to ethical and logistical issues, the program can expand the living donor liver pool and facilitate a greater number of living donor liver transplantations. The study involved simultaneous performance of 4 major operations, which posed a challenging task for the transplant team. However, donor survival rate was 100% and baseline clinical parameters and postoperative complications were comparable between different groups.
Article
Medicine, General & Internal
Alessandra Cristaudi, Ignazio Tarantino, Andreas Scheiwiller, Andrea Wiencierz, Pietro Majno-Hurst, Bruno M. Schmied, Juerg Metzger, Mark Hartel, Michael Kremer, Giulia Manzini
Summary: The study proposes a multicentric randomized controlled trial to compare the effectiveness of the white test in reducing postoperative bile leakage.
Article
Materials Science, Biomaterials
Muhammad Rizwan
Summary: Liver tissue engineering aims to incorporate functional bile ducts in organoid models for more accurate disease modeling. This article discusses the challenges and potential solutions, emphasizing the importance of bile ducts in mimicking bile-duct related diseases.
Review
Gastroenterology & Hepatology
Jeremy Lotto, Tabea L. Stephan, Pamela A. Hoodless
Summary: Advancements in single-cell technologies and lineage tracing have enhanced our understanding of liver development. This review explores the formation of different types of liver cells and highlights the similarities between early liver development and the pathogenesis of liver injury. The research has significantly advanced our knowledge of cell differentiation, fate decisions, and the signaling microenvironment in liver development. This understanding also provides insights into liver disease and cancer and offers potential for improving regenerative medicine strategies.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Anatomy & Morphology
Hiromu Fujisawa, Noriaki Ota, Nobuyoshi Shiojiri
Summary: The present study revealed that Inv genes play a crucial role in the development of bile and pancreatic ducts. The absence of Inv genes in mice led to anomalies in the polarity of intrahepatic bile ducts and ductules, as well as the lack of main pancreatic duct formation and morphological polarity. These findings suggest that Inv genes are necessary for the establishment of planar cell polarity in the liver and pancreas.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Cell Biology
Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, Jose Ignacio Valenzuela, Hernan Andres Morales-Navarrete, Christian Franke, Helin Raeaegel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis L. Kalaidzidis, Timofei Zatsepin, Marino Zerial
Summary: The morphogenesis of bile canaliculi in the liver is determined by the interplay between molecular pathways and mechanical forces, with hepatocytes forming specific extensions of the apical membrane that ensure anisotropic expansion of the lumen. Silencing the Rab35 gene leads to loss of apical bulkheads and cyst formation, indicating the essential role of these structures in liver tissue morphogenesis. The reengineering of hepatocyte polarity to convert bile canaliculi into epithelial tubes suggests that apical bulkheads are intrinsic mechanical elements determining the elongation of bile canaliculi during liver tissue development.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Xinbei Tian, Ying Wang, Ying Lu, Bo Wu, Shanshan Chen, Jun Du, Wei Cai, Yongtao Xiao
Summary: Biliary atresia (BA) is a liver disease in neonates characterized by obstructed bile ducts. The lack of early diagnostic markers and understanding of its pathogenesis has led to high mortality rates. This study found that D-2-hydroxyglutarate (D-2-HG) levels were elevated in the plasma and liver of BA patients and correlated with liver injuries. D-2-HG inhibited liver organoid growth and mitochondrial respiration, while increasing aerobic glycolysis. These findings suggest that D-2-HG may serve as a diagnostic biomarker and therapeutic target for BA.
CELL DEATH & DISEASE
(2022)
Article
Surgery
Davide Citterio, Marta Vaiani, Carlo Sposito, Roberta Elisa Rossi, Maria Flores, Carlo Battiston, Vincenzo Mazzaferro
Summary: This study shows that gadoxetic acid disodium-enhanced magnetic resonance cholangiography is highly accurate in detecting and locating postoperative biliary leaks, especially in peripheral locations, reducing the need for invasive cholangiography by 50%. Patients with peripheral leaks can avoid invasive procedures and have shorter hospital stays when managed conservatively.
Article
Pathology
Soo-Jin Cho, Emily R. Perito, Nafis Shafizadeh, Grace E. Kim
Summary: Neonatal cholestatic liver disease is rare and complex, requiring close collaboration between pathologists and pediatric gastroenterologists for accurate diagnosis. The dialogue should begin early, before obtaining a liver biopsy, and continue through the final pathologic diagnosis, integrating clinical, laboratory, imaging, and genetic data. The focus is on non-biliary atresia causes of neonatal cholestasis, including infectious, genetic, and metabolic factors.
Article
Medicine, General & Internal
Xiu-Ping Bai, Yong-Mei Fan, Lei Zhang, Guo-Hua Yang, Xing Li
Summary: The relationship between cirrhosis and diabetes is controversial. The study found that in different periods of cirrhosis, fasting glucose and 2 h postprandial glucose levels changed in different amplitudes. The concentration of glycogen and the activity of G6P in the liver decreased, leading to insulin resistance in mice and a reduction in islet areas. The NF-kappa B pathway may play a role in this process.
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
(2021)
Article
Cell Biology
Laura M. Molina, Junjie Zhu, Qin Li, Tirthadipa Pradhan-Sundd, Yekaterina Krutsenko, Khaled Sayed, Nathaniel Jenkins, Ravi Vats, Bharat Bhushan, Sungjin Ko, Shikai Hu, Minakshi Poddar, Sucha Singh, Junyan Tao, Prithu Sundd, Aatur Singhi, Simon Watkins, Xiaochao Ma, Panayiotis Benos, Andrew Feranchak, George Michalopoulos, Kari Nejak-Bowen, Alan Watson, Aaron Bell, Satdarshan P. Monga
Summary: YAP1 plays a key role in bile duct development, while hepatocytes achieve adaptation through reduced metabolic and synthetic function to survive for 8 months, blocking the formation of the biliary tree.
Review
Medicine, General & Internal
Pierre-Antoine Soret, Julie Magusto, Chantal Housset, Jeremie Gautheron
Summary: NAFLD, associated with obesity and metabolic syndrome, is a common liver disease but lacks approved pharmacological treatments for NASH. Ongoing preclinical research is improving our understanding of NAFLD pathophysiology and identifying new therapeutic targets through various models.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Amel Ben Saad, Virginie Vauthier, Agota Toth, Angelika Janaszkiewicz, Anne-Marie Durand-Schneider, Alix Bruneau, Jean-Louis Delaunay, Martine Lapalus, Elodie Mareux, Isabelle Garcin, Emmanuel Gonzales, Chantal Housset, Tounsia Ait-Slimane, Emmanuel Jacquemin, Florent Di Meo, Thomas Falguieres
Summary: Certain CFTR correctors can rescue the maturation and canalicular localization of ABCB4 variants, but do not restore their secretion activity and also inhibit the activity of wild type ABCB4. In silico molecular docking analyses suggest direct interaction of these correctors with the transporter's transmembrane domains and ATP-binding sites.
LIVER INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Pasquale Piccolo, Rosa Ferriero, Anna Barbato, Sergio Attanasio, Marcello Monti, Claudia Perna, Florie Borel, Patrizia Annunziata, Annamaria Carissimo, Rossella De Cegli, Luca Quagliata, Luigi M. Terracciano, Chantal Housset, Jeffrey H. Teckman, Christian Mueller, Nicola Brunetti-Pierri
Summary: AAT deficiency is caused by pathogenic variants in the SERPINA1 gene, with the Z allele encoding for Z alpha 1-antitrypsin leading to hepatotoxic polymers. The up-regulation of miR-34b/c in PiZ mouse livers is correlated to intrahepatic ATZ, and its expression is dependent on JNK phosphorylation on Ser574. Deletion of miR-34b/c in PiZ mice results in early liver fibrosis and increased signaling of platelet-derived growth factor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Ester Gonzalez-Sanchez, Haquima El Mourabit, Marion Jager, Marie Clavel, Sophie Moog, Javier Vaquero, Tatiana Ledent, Axelle Cadoret, Jeremie Gautheron, Laura Fouassier, Dominique Wendum, Nicolas Chignard, Chantal Housset
Summary: The study showed that VDR signaling has an anti-inflammatory role in cholangiocytes and cholangiopathy, while PDIA3-mediated effects of vitamin D and its analogs also have anti-inflammatory effects in these settings.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Medicine, General & Internal
Lin Lei, Haquima Ei Mourabit, Chantal Housset, Axelle Cadoret, Sara Lemoinne
Summary: Non-alcoholic fatty liver disease (NAFLD) is associated with liver angiogenesis, which may lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Research has shown that angiogenesis plays a crucial role in the progression of NAFLD, and targeting angiogenesis, particularly VEGF, could be a potential treatment for NAFLD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Amel Ben Saad, Virginie Vauthier, Martine Lapalus, Elodie Mareux, Evangeline Bennana, Anne-Marie Durand-Schneider, Alix Bruneau, Jean-Louis Delaunay, Emmanuel Gonzales, Chantal Housset, Tounsia Ait-Slimane, Francois Guillonneau, Emmanuel Jacquemin, Thomas Falguieres
Summary: ABCB4 is an ABC transporter crucial for phosphatidylcholine secretion into bile. Research has identified RAB10 as a novel molecular partner of ABCB4, influencing its plasma membrane expression and function. Understanding the interactions between RAB10 and ABCB4 may lead to the development of novel therapies for liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Charlotte Bouzbib, Haquima El Mourabit, Dominique Wendum, Elisabeth Lasnier, Sarah Mouri, Chantal Housset, Dominique Thabut, Nicolas Weiss, Marika Rudler
Summary: The pathophysiology of acute encephalopathy in cirrhotic patients is not fully understood. Recent studies have indicated increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy. This study focused on the modification of ATP-binding cassette (ABC) transporters in the BBB and found a possible association between the expression of MRP5 and drug-induced acute encephalopathy in cirrhosis.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Augustin Schaefer, Martin Journaux, Haquima El Mourabit, Sarah Mouri, Dominique Wendum, Elisabeth Lasnier, Pierre-Olivier Couraud, Chantal Housset, Dominique Thabut, Marika Rudler, Nicolas Weiss
Summary: The study found that the plasma of cirrhotic patients with HE enhances leukocyte TEM across the hCMEC/D3 BBB model. There was a correlation between U937 TEM, West-Haven score, and ammonemia. A trend towards a correlation between U937 TEM and PS-100Beta in plasma, a marker of increased BBB permeability, was also observed.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Review
Pharmacology & Pharmacy
Juan Wang, Emilien Loeuillard, Gregory J. Gores, Sumera I. Ilyas
Summary: Cholangiocarcinoma (CCA) is a dense and desmoplastic tumor with a rich tumor microenvironment (TME) characterized by interactions between cancer cells and their surroundings, which can shape treatment response and resistance. TME targeting therapies have been evaluated in preclinical and clinical studies, showing potential as therapeutic targets for a subset of patients.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Gastroenterology & Hepatology
Lin Lei, Alix Bruneau, Haquima El Mourabit, Justine Guegan, Trine Folseraas, Sara Lemoinne, Tom Hemming Karlsen, Benedicte Hoareau, Romain Morichon, Ester Gonzalez-Sanchez, Claire Goumard, Vlad Ratziu, Pierre Charbord, Jeremie Gautheron, Frank Tacke, Thierry Jaffredo, Axelle Cadoret, Chantal Housset
Summary: This study identified portal mesenchymal progenitors of myofibroblasts in liver fibrosis and revealed their role in myofibroblast formation. Portal mesenchymal progenitors play a crucial role in the formation of fibrotic septa, along with neovessels and HSC-MFs that arise from a preexisting pool.
Article
Gastroenterology & Hepatology
Bolni Marius Nagalo, Yumei Zhou, Emilien J. Loeuillard, Chelsae Dumbauld, Oumar Barro, Alexander T. Baker, Mansi Arora, James M. Bogenberger, Natalie Meurice, Joachim Petit, Pedro Luiz Serrano Uson, Faaiq Asiam, Elizabeth Raupach, Musa Gabere, Alexei Basnakian, Camila C. Simoes, Martin J. Cannon, Steven R. Post, Kenneth Buetow, Jean Christopher Chamcheu, Michael T. Barrett, Dan G. Duda, Bertram Jacobs, Richard Vile, Michael A. Barry, Lewis R. Roberts, Sumera Llyas, Mitesh J. Borad
Summary: This study demonstrates that wild-type Morreton virus has potential therapeutic effects on cholangiocarcinoma and hepatocellular carcinoma in vitro models. It can induce immune responses and lead to tumor regression. These findings support further development and clinical translation of Morreton virus as an oncolytic virotherapy platform.
Article
Gastroenterology & Hepatology
Thierry Poynard, Jean Marc Lacombe, Olivier Deckmyn, Valentina Peta, Sepideh Akhavan, Victor de Ledinghen, Fabien Zoulim, Didier Samuel, Philippe Mathurin, Vlad Ratziu, Dominique Thabut, Chantal Housset, Helene Fontaine, Stanislas Pol, Fabrice Carrat
Summary: This study validated a multianalyte blood test (LCR1-LCR2) in patients with chronic HCV, showing that the test can successfully identify patients with a very low risk of liver cancer within 5 years.
Meeting Abstract
Oncology
Emilien Loeuillard, Jingchun Yang, Haidong Dong, Gregory J. Gores, Sumera Ilyas