Article
Gastroenterology & Hepatology
Ehud Zigmond, Britta Franziska Zecher, Anna-Lena Bartels, Tomer Ziv-Baran, Thomas Roesch, Guido Schachschal, Ansgar W. Lohse, Hanno Ehlken, Christoph Schramm
Summary: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the biliary mucosa and colonization of the bile ducts with bacteria. This study found that the presence of Enterococci and Fungobilia in the bile ducts of PSC patients was associated with disease progression, highlighting the importance of microbiota-mucosal interaction in the pathogenesis of PSC.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bhargavi Nallamothu, Kaushik Kuche, Rohan Ghadi, Dasharath Chaudhari, Sanyog Jain
Summary: This study examines the impact of charge and chain length of bile salts in bilosomes on the oral bioavailability of insulin and verifies the results by examining their uptake via ASBT. The results indicate that anionic bilosomes are more efficiently taken up by ASBT than cationic bilosomes, thereby improving the oral bioavailability of insulin in bilosomes. Additionally, the developed bilosomes are able to provide superior protection in biological fluids while maintaining the integrity of the loaded drug.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Cell Biology
Tiffany Shi, Astha Malik, Annika Yang vom Hofe, Louis Matuschek, Mary Mullen, Celine S. Lages, Ramesh Kudira, Ruchi Singh, Wujuan Zhang, Kenneth D. R. Setchell, David Hildeman, Chandrashekhar Pasare, Brandee Wagner, Alexander G. Miethke
Summary: In this study, we found that activation of the nuclear receptor FXR by pharmacological agonists can reduce bile acid synthesis and suppress the production of inflammatory factors by inflammatory cells, thereby blocking the progression of liver bile duct injury. Deletion of FXR leads to abnormal responses in T(H)1 and T(H)17 lymphocytes, making mice resistant to the therapeutic effects of FXR agonist treatment. Therefore, hepatic macrophages are potential targets for the treatment of cholestatic liver diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
Min Wen, Yubei Liu, Ruiying Chen, Ping He, Feihua Wu, Rui Li, Yining Lin
Summary: This study found that Geniposide could effectively delay the progression of sclerosing cholangitis by modulating inflammation, fibrosis, and bile acid homeostasis in a mouse model.
PHYTOTHERAPY RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Aristeidis Grigoriadis, Kristina Imeen Ringe, Johan Bengtsson, Erik Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, Annika Bergquist
Summary: Magnetic resonance cholangiopancreatography (MRCP) plays an important role in the prognosis assessment of primary sclerosing cholangitis (PSC). A novel, simple, and reproducible risk-score (DiStrict score) based on MRCP findings was developed and showed a strong association with prognosis in individuals with PSC. This score can be easily used in clinical practice and has the potential to be useful in clinical trials and patient counseling and management.
Article
Chemistry, Multidisciplinary
Feiyang Deng, Kyoung Sub Kim, Jiyoung Moon, You Han Bae
Summary: Bile acid-modified nanoparticles can improve oral bioavailability of poorly permeable drugs by interacting with bile acid transporters. This study investigates the transport of glycocholic acid (GCA)-conjugated polystyrene nanoparticles (GCPNs) in Caco-2 cell models and identifies a new pathway correlated with both apical sodium-dependent bile acid transporter (ASBT) and chylomicron pathways. The study also reveals that the higher uptake of GCPNs does not result in higher transcytosis compared to unmodified nanoparticles (CPNs). Pharmacological and genomics analysis indicate that GCA conjugation alters endocytosis mechanisms and downregulates cellular response, leading to higher cellular retention of GCPNs.
Article
Multidisciplinary Sciences
Mary Ayers, Silvia Liu, Aatur D. Singhi, Karis Kosar, Pamela Cornuet, Kari Nejak-Bowen
Summary: In this study, the clinical relevance of beta-catenin localization in patients with primary sclerosing cholangitis (PSC) was investigated. The results suggest that changes in beta-catenin expression and activation during the progression of PSC may serve as a useful prognostic tool for predicting disease recurrence.
SCIENTIFIC REPORTS
(2022)
Article
Gastroenterology & Hepatology
Roni F. Kunst, Dirk R. de Waart, Frank Wolters, Suzanne Duijst, Esther W. Vogels, Isabelle Bolt, Joanne Verheij, Ulrich Beuers, Ronald P. J. Oude Elferink, Stan F. J. van de Graaf
Summary: This study demonstrates that reducing the bile salt pool size effectively lowers cholestatic liver injury in mice. Systemic ASBT inhibition may be a valuable treatment for cholestatic liver disease by decreasing the pool size and increasing renal bile salt output, even under conditions of minimal fecal bile salt secretion.
Article
Multidisciplinary Sciences
Agnieszka Kempinska-Podhorodecka, Monika Adamowicz, Ewa Ostrycharz, Mateusz Chmielarz, Maciej Wojcicki, Piotr Milkiewicz, Malgorzata Milkiewicz
Summary: The study found that miR-506 is significantly upregulated in the colon of patients with PSC and PSC+UC, but downregulated in patients with UC. This differential expression may be associated with phenotypic presentations of colonic inflammation and neoplasia. Upregulation of miR-506 in PSC and PSC+UC patients may lead to failure of bicarbonate secretion and inhibition of p53, while downregulation of miR-506 in UC patients enhances S1P production, leading to pro-inflammatory signaling.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Katsuyuki Miyabe, Vinay Chandrasekhara, Nicha Wongjarupong, Jun Chen, Lu Yang, Stephen Johnson, Nicholas Chia, Marina Walther-Antonio, Janet Z. Yao, Sean C. Harrington, Cynthia K. Nordyke, John E. Eaton, Andrea A. Gossard, Sharad Oli, Hamdi A. Ali, Sravanthi Lavu, Nasra H. Giama, Fatima A. Hassan, Hawa M. Ali, Felicity T. Enders, Sumera I. Ilyas, Gregory J. Gores, Mark D. Topazian, Purna C. Kashyap, Lewis R. Roberts
Summary: This study investigated the microbiota profiles in bile and stool samples of patients with PSC and CCA, and found that bile and stool have different microbiota profiles. The abundance of Fusobacteria in bile was correlated with the duration of PSC in CCA patients. These findings suggest a potential role for microbiota-driven inflammation in the pathogenesis of perihilar CCA.
Review
Gastroenterology & Hepatology
Natassia Tan, John Lubel, William Kemp, Stuart Roberts, Ammar Majeed
Summary: Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease characterized by inflammatory biliary strictures. The pathophysiology of PSC is poorly understood, but it is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures. Currently, there is no proven medical therapy to alter disease progression in PSC, and liver transplantation is the only option for end-stage liver disease. Manipulation of the gut microbiome and bile acid metabolism show promise in phase II trials. Statins and aspirin may reduce the risk of malignancy in PSC patients. Balloon dilatation is safer and equally effective compared to biliary stent insertion for clinically relevant strictures.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Nora Cazzagon, Ester Gonzalez-Sanchez, Haquima El-Mourabit, Dominique Wendum, Dominique Rainteau, Lydie Humbert, Christophe Corpechot, Olivier Chazouilleres, Lionel Arrive, Chantal Housset, Sara Lemoinne
Summary: In patients with primary sclerosing cholangitis (PSC), the gallbladder status affects bile acid homeostasis and disease features. Evidence suggests less bile acid toxicity in patients with enlarged gallbladders and increased disease severity in those who had undergone cholecystectomy. In a mouse model of PSC, cholecystectomy worsened cholangitis and liver fibrosis. Overall, the gallbladder plays a protective role in PSC.
Article
Gastroenterology & Hepatology
Amanda Ricciuto, Binita M. Kamath, Gideon M. Hirschfield, Palak J. Trivedi
Summary: Autoimmune liver diseases are classified into three syndromes, but they are challenging due to variant presentations and lack of definable disease aetiologies. This article argues that "autoimmune sclerosing cholangitis" and "PSC/AIH-overlap" in young patients represent inflammatory phases of primary sclerosing cholangitis and should be considered as the same entity to facilitate unified care and collaborative studies.
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Maria Reich, Lina Spomer, Caroline Klindt, Katharina Fuchs, Jan Stindt, Kathleen Deutschmann, Johanna Hohne, Evaggelia Liaskou, Johannes R. Hov, Tom H. Karlsen, Ulrich Beuers, Joanne Verheij, Sofia Ferreira-Gonzalez, Gideon Hirschfield, Stuart J. Forbes, Christoph Schramm, Irene Esposito, Dirk Nierhoff, Peter Fickert, Claudia Daniela Fuchs, Michael Trauner, Maria Garcia-Beccaria, Gisela Gabernet, Sven Nahnsen, Jan-Philipp Mallm, Marina Vogel, Kristina Schoonjans, Tobias Lautwein, Karl Koehrer, Dieter Haeussinger, Tom Luedde, Mathias Heikenwalder, Verena Keitel
Summary: The study revealed that reduced levels of TGR5 in BECs from patients with PSC and Abcb4(-/-) mice promote the development of a reactive BEC phenotype, aggravate biliary injury, and contribute to the pathogenesis of sclerosing cholangitis. Restoration of biliary TGR5-expression levels represents a previously unknown mechanism of action of norUDCA.
JOURNAL OF HEPATOLOGY
(2021)
Review
Gastroenterology & Hepatology
Michal Prokopic, Ulrich Beuers
Summary: PSC is a rare liver disease characterized by bile duct abnormalities leading to liver fibrosis and potential cholangiocarcinoma. The exact pathogenesis is still unclear, with strong association with inflammatory bowel disease. Current medical treatments have not been proven effective, with liver transplantation remaining the most viable option for late-stage disease.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Mathias Jachs, Lukas Hartl, Benedikt Simbrunner, David Bauer, Rafael Paternostro, Bernhard Scheiner, Lorenz Balcar, Georg Semmler, Albert Friedrich Staettermayer, Matthias Pinter, Peter Quehenberger, Michael Trauner, Thomas Reiberger, Mattias Mandorfer
Summary: Baveno VII proposed criteria for clinically significant portal hypertension in compensated advanced chronic liver disease (cACLD) but many patients remain unclassified. The sequential application of VITRO decreased the number of unclassified patients and improved prognostication.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuen Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagstrom, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis
Summary: Modulating the expression of angiotensin-converting enzyme 2 (ACE2) through farnesoid X receptor (FXR) can reduce susceptibility to SARS-CoV-2 infection, as shown in various tissues and organoids in vitro, in vivo, and ex vivo. The use of z-guggulsterone and ursodeoxycholic acid (UDCA) can downregulate ACE2 and decrease viral infection, including in the nasal epithelium. Clinical data also indicate positive outcomes with UDCA treatment in SARS-CoV-2 infection. These findings suggest that targeting the FXR-ACE2 pathway could be a potential strategy for preventing COVID-19.
Article
Gastroenterology & Hepatology
Benedikt Simbrunner, Esther Caparros, Teresa Neuwirth, Philipp Schwabl, Philipp Koenigshofer, David Bauer, Rodrig Marculescu, Michael Trauner, Bernhard Scheiner, Georg Stary, Mattias Mandorfer, Thomas Reiberger, Ruben Frances
Summary: In patients with advanced chronic liver disease (ACLD), bacterial translocation (BT) leads to systemic inflammation and circulatory dysfunction, but there is no clear correlation between BT markers and portal hypertension and circulatory dysfunction.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Nikolaus Pfisterer, Michael Schwarz, Mathias Jachs, Florian Putre, Lukas Ritt, Mattias Mandorfer, Christian Madl, Michael Trauner, Thomas Reiberger
Summary: Prophylactic endoscopic band ligation (EBL) is a safe procedure to prevent variceal bleeding in cirrhotic patients, even in the presence of thrombocytopenia or high INR. The risk of EBL-related bleeding is mainly associated with high MELD and bilirubin levels, but not with platelet count, INR, or non-selective beta-blocker use.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Immunology
Mihael Vucur, Ahmed Ghallab, Anne T. Schneider, Arlind Adili, Mingbo Cheng, Mirco Castoldi, Michael T. Singer, Veronika Buettner, Leonie S. Keysberg, Lena Kuesgens, Marlene Kohlhepp, Boris Goerg, Suchira Gallage, Jose Efren Barragan Avila, Kristian Unger, Claus Kordes, Anne-Laure Leblond, Wiebke Albrecht, Sven H. Loosen, Carolin Lohr, Markus S. Joerdens, Anne Babler, Sikander Hayat, David Schumacher, Maria T. Koenen, Olivier Govaere, Mark Boekschoten, Simone Joers, Carlos Villacorta-Martin, Vincenzo Mazzaferro, Josep M. Llovet, Ralf Weiskirchen, Jakob N. Kather, Patrick Starlinger, Michael Trauner, Mark Luedde, Lara R. Heij, Ulf P. Neumann, Verena Keitel, Johannes G. Bode, Rebekka K. Shneider, Frank Tacke, Bodo Levkau, Twan Lammers, Georg Fluegen, Theodore Alexandrov, Amy L. Collins, Glyn Nelson, Fiona Oakley, Derek A. Mann, Christoph Roderburg, Thomas Longerich, Achim Weber, Augusto Villanueva, Andre L. Samson, James M. Murphy, Rafael Kramann, Fabian Geisler, Ivan G. Costa, Jan G. Hengstle, Mathias Heikenwalder, Tom Luedde
Summary: A molecular switch in hepatocytes can reprogram between two forms of necroptosis signaling, which fundamentally impacts immune responses and hepatocarcinogenesis.
Article
Gastroenterology & Hepatology
Mathias Jachs, Raphael Sauberer, Alexander Stiegler, Anton Dechene, Raphael Tazreiter, Lukas Hartl, David Bauer, Lorenz Balcar, Robert Strassl, Mattias Mandorfer, Michael Trauner, Petra Munda, Peter Ferenci, Thomas Reiberger
Summary: A study conducted at Vienna General Hospital assessed the treatment eligibility and uptake in chronic hepatitis B (CHB) patients. They found that 9.2% of patients had severe fibrosis/cirrhosis, and 23.4%-29.5% met current treatment recommendations. The treatment uptake among eligible patients was high at 79.8%-89.2%.
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2023)
Article
Gastroenterology & Hepatology
Lorenz Balcar, Julia Krawanja, Bernhard Scheiner, Rafael Paternostro, Benedikt Simbrunner, Georg Semmler, Mathias Jachs, Lukas Hartl, Albert Friedrich Staettermayer, Philipp Schwabl, Matthias Pinter, Thomas Szekeres, Michael Trauner, Thomas Reiberger, Mattias Mandorfer
Summary: A recent study investigated the prognostic value of venous ammonia levels for liver-related outcomes while considering portal hypertension and systemic inflammation severity. Venous ammonia was found to predict hepatic decompensation, non-elective liver-related hospitalisation, acute-on-chronic liver failure, and liver-related death.
Article
Gastroenterology & Hepatology
Lukas Hartl, Benedikt Simbrunner, Mathias Jachs, Peter Wolf, David Josef Maria Bauer, Bernhard Scheiner, Lorenz Balcar, Georg Semmler, Michael Schwarz, Rodrig Marculescu, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Summary: This study investigated the pituitary-adrenal axis in patients with cirrhosis at different clinical stages and examined the clinical impact of decreased serum cortisol levels in stable patients with advanced chronic liver disease (ACLD). The results showed that the pituitary-ACTH-adrenal-cortisol axis is progressively suppressed with increasing severity of cirrhosis. Lower total cortisol levels were independently associated with a higher risk of adverse clinical outcomes, including bacterial infections, further decompensation, acute-on-chronic liver failure, and liver-related death.
Article
Gastroenterology & Hepatology
Rafael Paternostro, Mathias Jachs, Lukas Hartl, Benedikt Simbrunner, Bernhard Scheiner, David Bauer, Philipp Schwabl, Georg Semmler, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Summary: Non-selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD), but metabolic co-morbidities (MetC) have an impact on the haemodynamic effects of NSBB and hepatic decompensation in cACLD patients.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Tomas Machacek, Claudia D. Fuchs, Franziska Winkelmann, Marcus Frank, Hubert Scharnagl, Tatjana Stojakovic, Martina Sombetzki, Michael Trauner
Summary: In this study, the researchers evaluated the effect of polyhydroxylated bile acids (BAs) on the inflammation and fibrosis caused by Schistosoma mansoni infection. They found that mice lacking the Bsep gene showed less hepatic inflammation and fibrosis after infection, which could be attributed to the changes in bile acid composition and blood pH resulting from the loss of Bsep gene, affecting parasite fecundity and thus attenuating the development of S. mansoni-induced hepatic inflammation and fibrosis.
LIVER INTERNATIONAL
(2023)
Article
Medicine, General & Internal
Mattias Mandorfer, Elmar Aigner, Manfred Cejna, Arnulf Ferlitsch, Christian Datz, Tilmann Grater, Ivo Graziadei, Michael Gschwantler, Stephanie Hametner-Schreil, Harald Hofer, Mathias Jachs, Alexander Loizides, Andreas Maieron, Markus Peck-Radosavljevic, Florian Rainer, Bernhard Scheiner, Georg Semmler, Lukas Reider, Silvia Reiter, Maria Schoder, Rainer Schofl, Philipp Schwabl, Vanessa Stadlbauer, Rudolf Stauber, Elisabeth Tatscher, Michael Trauner, Alexander Ziachehabi, Heinz Zoller, Peter Fickert, Thomas Reiberger
Summary: The Billroth IV consensus was developed in Vienna on November 26, 2022, during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (oGGH) and the Austrian Society of Interventional Radiology (oGIR). Based on international recommendations and recent landmark studies, this consensus provides guidance on the diagnosis and management of portal hypertension in advanced chronic liver disease.
WIENER KLINISCHE WOCHENSCHRIFT
(2023)
Article
Gastroenterology & Hepatology
Claudia D. Fuchs, Natalie Sroda, Hubert Scharnagl, Ruchi Gupta, Wesley Minto, Tatjana Stojakovic, John T. Liles, Grant Budas, David Hollenback, Michael Trauner
Summary: This study demonstrates that cilofexor, a non-steroidal FXR agonist, improves cholestatic liver injury and hepatic fibrosis in the Mdr2-/-mouse model of sclerosing cholangitis. These findings suggest the potential therapeutic properties of cilofexor in cholestatic liver diseases, mediated by intestinal FXR-mediated gut-liver signaling.
Article
Gastroenterology & Hepatology
Christoph Grander, Moritz Meyer, Daniel Steinacher, Thierry Claudel, Bela Hausmann, Petra Pjevac, Felix Grabherr, Georg Oberhuber, Manuel Grander, Natascha Brigo, Almina Jukic, Julian Schwarzler, Guenter Weiss, Timon E. Adolph, Michael Trauner, Herbert Tilg
Summary: This study found a protective effect of NorUDCA in experimental alcoholic liver disease, which can reduce liver injury, decrease the expression of hepatic pro-inflammatory cytokines, and affect gut microbial commensalism.
Article
Gastroenterology & Hepatology
Claudia D. Fuchs, Thierry Claudel, Veronika Mlitz, Alessandra Riva, Moritz Menz, Ksenia Brusilovskaya, Felix Haller, Maximilian Baumgartner, Philipp Koenigshofer, Lukas W. Unger, Wilhelm Sjoeland, Hubert Scharnagl, Tatjana Stojakovic, Georg Busslinger, Thomas Reiberger, Hanns-Ulrich Marschall, Michael Trauner
Summary: The GLP-2 analogue teduglutide has hepatoprotective and antifibrotic effects in a mouse model of sclerosing cholangitis. GLP-2 treatment decreases hepatic inflammation and fibrosis, and activates the intestinal FXR-FGF15/19 signaling axis, resulting in reduced expression of Cyp7a1 and increased expression of Cyp2c70 in the liver, contributing to its protective effects.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
