Review
Biochemistry & Molecular Biology
Ji-Won Park, Jung-Hee Kim, Sung-Eun Kim, Jang Han Jung, Myoung-Kuk Jang, Sang-Hoon Park, Myung-Seok Lee, Hyoung-Su Kim, Ki Tae Suk, Dong Joon Kim
Summary: Cholangiopathies are various biliary diseases that affect the biliary epithelium and can lead to cholestasis and liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults, with research focusing on genetic risk, epigenetic changes, dysregulated mucosal immunity, and altered biliary epithelial cell function. Understanding the molecular pathogenesis of these diseases can help clinicians prevent and treat them more effectively.
Article
Gastroenterology & Hepatology
Roopa H. Nanjundappa, Urs Christen, Channakeshava S. Umeshappa
Summary: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two major autoimmune liver diseases. PBC primarily affects intrahepatic small bile duct epithelial cells in women, while PSC mainly affects medium and big bile duct epithelial cells in men. Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes and is more prevalent in PSC patients than in PBC patients. Understanding the immune surveillance mechanisms that differentiate between PBC and PSC patients is crucial for developing effective therapies and early diagnosis of CCA.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Roopa H. Nanjundappa, Urs Christen, Channakeshava S. Umeshappa
Summary: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two significant autoimmune liver diseases. PBC primarily affects small bile duct epithelial cells in women, while PSC predominantly affects medium and large intrahepatic and extrahepatic bile duct epithelial cells in men. Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes and its incidence is increasing worldwide. Although PBC patients rarely develop CCA compared to PSC patients, understanding the differences in immune surveillance mechanisms is crucial for effective diagnosis and treatment.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Raanan Greenman, Michal Segal-Salto, Neta Barashi, Ophir Hay, Avi Katav, Omer Levi, Ilan Vaknin, Revital Aricha, Sarit Aharoni, Tom Snir, Inbal Mishalian, Devorah Olam, Johnny Amer, Ahmad Salhab, Rifaat Safadi, Yaakov Maor, Palak Trivedi, Christopher J. Weston, Francesca Saffioti, Andrew Hall, Massimo Pinzani, Douglas Thorburn, Amnon Peled, Adi Mor
Summary: CCL24 is involved in fibrosis and inflammation in liver and its inhibition can reduce liver injury. This study found that blocking CCL24 improves inflammation, fibrosis, and cholestasis in PSC, and reduces proliferation and senescence of cholangiocytes.
Article
Medicine, Research & Experimental
Nidhi Jalan-Sakrikar, Abid Anwar, Usman Yaqoob, Can Gan, Anthony B. Lagnado, Alexander Q. Wixom, Diana Jurk, Robert C. Huebert
Summary: This study investigated the mechanistic relationship between telomere damage and biliary fibrosis in primary sclerosing cholangitis (PSC). The results showed telomere attrition and reduced telomerase reverse transcriptase (TERT) expression in patients with PSC. Cellular models demonstrated that telomere dysfunction can lead to senescence and fibrosis, which can be rescued by modulating TERT levels.
Article
Gastroenterology & Hepatology
Tobias Poch, Jenny Krause, Christian Casar, Timur Liwinski, Laura Glau, Max Kaufmann, Annika E. Ahrenstorf, Leonard U. Hess, Annerose E. Ziegler, Gloria Martrus, Sebastian Lunemann, Marcial Sebode, Jun Li, Dorothee Schwinge, Christian F. Krebs, Andre Franke, Manuel A. Friese, Karl J. Oldhafer, Lutz Fischer, Marcus Altfeld, Ansgar W. Lohse, Samuel Huber, Eva Tolosa, Nicola Gagliani, Christoph Schramm
Summary: This study established an atlas of intrahepatic T cells in PSC, uncovering a previously unrecognized population of liver-resident naive-like T cells and revealing their propensity to develop into T(H)17 cells in PSC patients.
JOURNAL OF HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Burcin Oezdirik, Tobias Mueller, Alexander Wree, Frank Tacke, Michael Sigal
Summary: PSC is an immune-related cholangiopathy associated with high progression rates to end-stage liver disease and risk of various cancers. Emerging evidence suggests a link between gut microbiota and disease pathogenesis, with studies showing differences in the gut microbiome of PSC patients compared to healthy individuals and those with IBD. Further research is needed to understand the role of gut microbiota in PSC and related malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Takafumi Yamamoto, Kazuyuki Mizuno, Takanori Ito, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Takuya Ishikawa, Akira Kanamori, Satoshi Yasuda, Hidenori Toyoda, Kenji Yokota, Tetsunari Hase, Naoki Nishio, Osamu Maeda, Makoto Ishii, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Masatoshi Ishigami, Hiroki Kawashima
Summary: Immune-related sclerosing cholangitis (irSC) is a rare disease with unclear clinical characteristics. This study aimed to summarize the clinical features of irSC. Retrospective analysis of clinical data from 1,393 advanced malignancy patients treated with immune-checkpoint inhibitors revealed that eight patients (11.9%) developed irSC as an immune-related adverse event. Compared to the non-irSC group, patients with irSC had a non-hepatocellular liver injury, elevated inflammatory markers, and biliary enzymes at the onset of liver injury. Additionally, abdominal pain was a common symptom in irSC patients. Treatment for irSC was found to be refractory, with only two patients experiencing improvement in liver injury. Further imaging examination is recommended for detecting intractable irSC in cases with these characteristics.
INVESTIGATIONAL NEW DRUGS
(2023)
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.
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)
Article
Gastroenterology & Hepatology
Jessica Katharine Dyson, Alasdair Blain, Mark David Foster Shirley, Mark Hudson, Steven Rushton, David Emrys Jeffreys Jones
Summary: This study investigates the potential environmental contributors to autoimmune liver diseases (AILD) such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Significant spatial clustering of PBC and PSC patients was observed, with distinct risk profiles and associations with different environmental factors and socio-economic statuses identified. This suggests different triggers and alternative pathways determine the phenotypic expression of autoimmunity in the affected population.
Article
Surgery
Wisam Sbeit, Tawfik Khoury, Eran Goldin, Mahmud Mahamid
Summary: The study found that fully-covered metal stent (FCMS) was a safe and effective treatment option for patients with Primary Sclerosing Cholangitis (PSC) related refractory Dominant Strictures (DS).
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Review
Gastroenterology & Hepatology
Helen T. Smith, Andrea Ribeiro de Souza, April H. Thompson, Megan M. McLaughlin, John J. Dever, Julie A. Myers, Jing Voon Chen
Summary: This study conducted a systematic literature review to investigate the evidence supporting treatment decisions for cholestatic pruritus associated with PBC and PSC. The findings showed a lack of consistent and reproducible evidence on the efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leading physicians to rely on clinical experience for treatment selection.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Surgery
Yunlu Feng, Shengyu Zhang, Zehui Zheng, Xi Wu, Tao Guo, Qingwei Jiang, Qiang Wang, Dongsheng Wu, Aiming Yang
Summary: A newly established biliary inflammation scoring (BIS) method based on EUS images showed high sensitivity and specificity in distinguishing between IgG4-SC and CC. Endoscopic ultrasound (EUS) should be considered as a useful diagnostic procedure for patients suspected of having IgG4-SC.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2021)
Article
Medicine, General & Internal
Anne-Christin Beatrice Wilde, Lena Maria Greverath, Lara Marleen Steinhagen, Nina Wald de Chamorro, Elise Leicht, Janett Fischer, Toni Herta, Thomas Berg, Beate Preuss, Reinhild Klein, Frank Tacke, Tobias Mueller
Summary: This study found that the prevalence of mAChR3inh+ auto-antibodies is significantly higher in both PBC and PSC patients. PBC patients with mAChR3inh+ auto-antibodies have higher levels of certain parameters and tend to have lower response rates to UDCA treatment. However, there are no significant differences in laboratory findings between PSC patients with and without mAChR3inh+ auto-antibodies.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Annika Bergquist, Tobias J. Weismueller, Cynthia Levy, Christian Rupp, Deepak Joshi, Jeremy Shanika Nayagam, Aldo J. Montano-Loza, Ellina Lytvyak, Ewa Wunsch, Piotr Milkiewicz, Roman Zenouzi, Christoph Schramm, Nora Cazzagon, Annarosa Floreani, Ingalill Friis Liby, Miriam Wiestler, Heiner Wedemeyer, Taotao Zhou, Christian P. Strassburg, Eirini Rigopoulou, George Dalekos, Manasa Narasimman, Xavier Verhelst, Helena Degroote, Mette Vesterhus, Andreas E. Kremer, Bennet Buendgens, Fredrik Rorsman, Emma Nilsson, Kristin Kaasen Jorgensen, Erik von Seth, Martin Cornillet Jeannin, Nils Nyhlin, Harry Martin, Stergios Kechagias, Kristine Wiencke, Marten Werner, Benedetta Terziroli Beretta-Piccoli, Marco Marzioni, Helena Isoniemi, Johanna Arola, Agnes Wefer, Jonas Soderling, Martti Farkkila, Henrike Lenzen
Summary: This study compares different follow-up strategies in patients with PSC and finds that scheduled imaging can improve survival. There are considerable variations in follow-up strategies across centers, but multiple factors may contribute to this result.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Muyiwa Awoniyi, Jeremy Wang, Billy Ngo, Vik Meadows, Jason Tam, Amba Viswanathan, Yunjia Lai, Stephanie Montgomery, Morgan Farmer, Martin Kummen, Louise Thingholm, Christoph Schramm, Corinna Bang, Andre Franke, Kun Lu, Huiping Zhou, Jasmohan S. Bajaj, Phillip B. Hylemon, Jenny Ting, Yury Popov, Johannes Roksund Hov, Heather L. Francis, Ryan Balfour Sartor
Summary: By studying the microbial composition in germ-free and antibiotic-treated mice and PSC patients, we identified different bacterial species with functional protective and detrimental effects in these animals and patients, which are associated with clinical risk scores. These findings are important for the development of personalized therapeutic approaches.
Article
Gastroenterology & Hepatology
Christopher L. Bowlus, Lionel Arrive, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Gonzalo Sapisochin, Rachna Shroff, James H. Tabibian, David N. Assis
Article
Gastroenterology & Hepatology
Mikal Jacob Hole, Kristin Kaasen Jorgensen, Kristian Holm, Peder R. Braadland, Malin Holm Meyer-Myklestad, Asle Wilhelm Medhus, Dag Henrik Reikvam, Alexandra Gotz, Krzysztof Grzyb, Kirsten Muri Boberg, Tom Hemming Karlsen, Martin Kummen, Johannes R. Hov
Summary: This study investigated the characteristics of the gut microbiota in patients with primary sclerosing cholangitis (PSC) and found several features associated with PSC, including an expansion of Proteobacteria and increased variability. Furthermore, certain genera and the presence of the pathobiont Klebsiella were associated with reduced survival in PSC patients, and concomitant inflammatory bowel disease (IBD) was associated with reduced levels of Akkermansia.
Article
Allergy
Mari Kaarbo, Mingyi Yang, Johannes R. Hov, Kristian Holm, Mirta Mittelstedt Leal de Sousa, Magnhild E. Macpherson, Henrik M. Reims, Anne-Marte Bakken Kran, Bente Halvorsen, Tom H. Karlsen, Pal Aukrust, Knut E. A. Lundin, Borre Fevang, Magner Bjoras, Silje Fjellgard Jorgensen
Summary: This study aimed to investigate the role of the duodenal microenvironment in the pathogenesis of duodenal inflammation in CVID. The findings suggest altered functions of the duodenal epithelium, particularly in response to lipopolysaccharide and viruses. Viruses, rather than gluten sensitivity, could be related to duodenal inflammation in CVID.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Ayodeji Awoyemi, Johannes R. Hov, Marius Troseid
CIRCULATION-HEART FAILURE
(2023)
Article
Infectious Diseases
Martin Hoenigl, Jon Salmanton-Garcia, Matthias Egger, Jean-Pierre Gangneux, Tihana Bicanic, Sevtap Arikan-Akdagli, Ana Alastruey-Izquierdo, Nikolai Klimko, Aleksandra Barac, Volkan Ozenci, Eelco F. J. Meijer, Nina Khanna, Matteo Bassetti, Riina Rautemaa-Richardson, Katrien Lagrou, Kai -Manuel Adam, Emin Halis Akalin, Murat Akova, Valentina Arsic Arsenijevic, Avinash Aujayeb, Ola Blennow, Stephane Bretagne, Francois Danion, Blandine Denis, Nick Alexander de Jonge, Guillaume Desoubeaux, Lubos Drgona, Nurettin Erben, Andrea Gori, Julio Garcia Rodriguez, Carolina Garcia-Vidal, Daniele Roberto Giacobbe, Anna L. Goodman, Petr Hamal, Helena Hammarstrom, Cristina Toscano, Fanny Lanternier, Cornelia Lass-Floerl, Deborah E. A. Lockhart, Thomas Longval, Laura Loughlin, Tadeja Matos, Malgorzata Mikulska, Manjusha Narayanan, Sonia Martin-Perez, Juergen Prattes, Benedict Rogers, Laman Rahimli, Maite Ruiz, Emmanuel Roilides, Michael Samarkos, Ulrike Scharmann, Uluhan Sili, Oguz Resat Sipahi, Alena Sivakova, Joerg Steinmann, Janina Trauth, Ozge Turhan, Jens Van Praet, Antonio Vena, P. Lewis White, Birgit Willinger, Anna Maria Tortorano, Maiken C. Arendrup, Philipp Koehler, Oliver A. Cornely
Summary: The European Confederation of Medical Mycology (ECMM) collected data on candidaemia patients in Europe to assess the association between adherence to guideline recommendations and outcomes. The study found that following the recommendations can improve the survival rate of patients.
LANCET INFECTIOUS DISEASES
(2023)
Review
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Summary: Our current understanding of human memory CD8(+) T cells mainly comes from studies of the intravascular space, but new data challenges some established ideas and suggests the need for conceptual revision. This review provides a brief history of the field and summarizes the biology of circulating and tissue-resident memory CD8(+) T cells, which play a crucial role in immune surveillance. The authors also discuss how future human studies can improve our understanding of CD8(+) T cells and inform the development of better immunotherapies and vaccines.
Editorial Material
Immunology
Barbara L. Shacklett, Marcus Buggert, Joana Dias
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Martin Cornillet, Helen Zemack, Hannes Jansson, Ernesto Sparrelid, Ewa Ellis, Niklas K. Bjorkstrom
Summary: Alpha-1 antitrypsin deficiency (A1ATD) is present in 10.8% of patients with biliary tract cancer (BTC), with no significant clinical differences compared to non-A1ATD BTC. The abundance of A1AT protein is increased in intrahepatic cholangiocarcinoma (iCCA) and is influenced by genomic alterations. A1ATD may be associated with a less aggressive phenotype, while high A1AT expression may contribute to a more aggressive phenotype.
Correction
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Correction
Immunology
Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. Vanbrocklin, Lael M. Yonker, E. John Wherry
Review
Immunology
Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. VanBrocklin, Lael M. Yonker, E. John Wherry
Review
Infectious Diseases
Jon Salmanton-Garcia, Martin Hoenigl, Jean-Pierre Gangneux, Esther Segal, Ana Alastruey-Izquierdo, Sevtap Arikan Akdagli, Katrien Lagrou, Volkan oezenci, Antonio Vena, Oliver A. Cornely
Summary: The diagnostic capacity for invasive fungal infections in Europe is generally good, but there are limitations in access to certain diagnostic tools and antifungal drugs. These limitations need to be addressed to ensure optimal diagnosis and treatment for all patients.
Article
Critical Care Medicine
Marius Troseid, Jan Cato Holter, Kristian Holm, Beate Vestad, Taisiia Sazonova, Beathe K. Granerud, Anne Ma Dyrhol-Riise, Aleksander R. Holten, Kristian Tonby, Anders Benjamin Kildal, Lars Heggelund, Anders Tveita, Simen Boe, Karl Erik Muller, Synne Jenum, Johannes R. Hov, Thor Ueland
Summary: The gut microbiota of hospitalized COVID-19 patients is altered, with reduced diversity and a different composition in those requiring intensive care unit (ICU) admission. This altered gut microbiota is associated with ICU admission and 60-day mortality. These findings suggest that gut microbiota alterations during hospitalization may be related to poor prognosis in severe COVID-19.
