Article
Gastroenterology & Hepatology
Hege Marie Vedeld, Marit M. Grimsrud, Kim Andresen, Heidi D. Pharo, Erik von Seth, Tom H. Karlsen, Hilde Honne, Vemund Paulsen, Martti A. Farkkila, Annika Bergquist, Marine Jeanmougin, Lars Aabakken, Kirsten M. Boberg, Trine Folseraas, Guro E. Lind
Summary: The study aimed to establish robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Using ddPCR analysis, high accuracy was achieved in detecting CCA in PSC patients, even up to 12 months before official diagnosis, indicating the potential of these biomarkers to complement current detection methods.
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
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
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
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
Gastroenterology & Hepatology
Christina Villard, Ingalill Friis-Liby, Fredrik Rorsman, Karouk Said, Anna Warnqvist, Martin Cornillet, Stergios Kechagias, Nils Nyhlin, Marten Werner, Izabella Janczewska, Therese Hagstrom, Emma Nilsson, Annika Bergquist
Summary: This study prospectively evaluated the effectiveness of yearly MRI/MRCP surveillance in detecting cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) and found it to be ineffective in detecting cancer early enough to support long-term survival. Personalized follow-up strategies and improved diagnostic methods for PSC-related CCA are needed.
JOURNAL OF HEPATOLOGY
(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
Gastroenterology & Hepatology
Serge Baroud, Alexander J. Sahakian, Tarek Sawas, Andrew C. Storm, John A. Martin, Barham K. Abu Dayyeh, Mark D. Topazian, Michael J. Levy, Lewis R. Roberts, Gregory J. Gores, Bret T. Petersen, Vinay Chandrasekhara
Summary: This study determined the performance characteristics of transpapillary biopsy sampling and fluorescence in situ hybridization in combination with standard brush cytology for diagnosing malignant biliary strictures. The findings suggest that trimodality sampling improves the diagnostic sensitivity for malignancy, but it is not superior to BC+FISH in patients with primary sclerosing cholangitis.
GASTROINTESTINAL ENDOSCOPY
(2022)
Article
Gastroenterology & Hepatology
Aiva Lundberg Bave, Annika Bergquist, Matteo Bottai, Anna Warnqvist, Erik von Seth, Caroline Nordenvall
Summary: The study found that PSC patients have a four times overall increased risk of developing cancer compared to the general population, with a particularly higher risk of developing hepatobiliary, colorectal, and pancreatic cancer.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
John E. Eaton, Christopher L. Welle, Zeinab Bakhshi, Shannon P. Sheedy, Ilkay S. Idilman, Gregory J. Gores, Charles B. Rosen, Julie K. Heimbach, Timucin Taner, Denise M. Harnois, Keith D. Lindor, Nicholas F. LaRusso, Andrea A. Gossard, Konstantinos N. Lazaridis, Sudhakar K. Venkatesh
Summary: This study aimed to evaluate the diagnostic performances and prognostic implications of ultrasound and MRI-based perihilar cholangiocarcinoma (CCA) detection among patients with primary sclerosing cholangitis (PSC). Results showed that MRI was superior to ultrasound for the detection of early-stage CCA in PSC patients, and identifying CCA before symptom onset with MRI was associated with improved outcomes.
Article
Oncology
Eline J. C. A. Kamp, Winand N. M. Dinjens, Michail Doukas, Ronald van Marion, Joanne Verheij, Cyriel Y. Ponsioen, Marco J. Bruno, Bas Groot Koerkamp, Palak J. Trivedi, Maikel P. Peppelenbosch, Annemarie C. de Vries
Summary: The carcinogenesis process of primary sclerosing cholangitis (PSC)-associated cholangiocarcinoma (CCA) is not well understood. This study aimed to evaluate the genetic alterations during the progression from biliary dysplasia to CCA in PSC patients. The results showed a variety of genetic alterations in PSC-CCA, with copy number variations (CNVs) being present early and mutations in ERBB2, TP53, and KRAS appearing later in the development of CCA. These findings hold promise for the development of diagnostic strategies guided by next-generation sequencing (NGS) in PSC-CCA.
JOURNAL OF PATHOLOGY
(2022)
Review
Medicine, General & Internal
Francesco Martini, Daniele Balducci, Martina Mancinelli, Valerio Buzzanca, Elena Fracchia, Giuseppe Tarantino, Antonio Benedetti, Marco Marzioni, Luca Maroni
Summary: Primary Biliary Cholangitis (PBC) is a liver disease with a varied presentation, progression, and response to treatment. Current risk assessment relies on analyzing demographic data, clinical findings, antibody profiles, and liver fibrosis evaluation to identify patients at higher risk of disease progression. The response to therapy after one year remains a significant factor influencing the prognosis of PBC patients. Tailored treatment strategies are emerging to replace the one-size-fits-all approach, requiring the development of risk prediction models to assess patients' course, outcome, and response to treatment at the time of diagnosis. This review provides an overview of current and emerging risk stratification tools and speculates on their potential impact on PBC management.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Gastroenterology & Hepatology
Atsushi Tanaka
Summary: Primary biliary cholangitis (PBC) is an autoimmune disease that mainly affects middle-aged women but also young women and men. It is characterized by degeneration and necrosis of intrahepatic biliary epithelial cells, with early diagnosis through detection of antimitochondrial antibodies and introduction of ursodeoxycholic acid as first-line treatment significantly improving clinical outcomes.
CLINICAL AND MOLECULAR HEPATOLOGY
(2021)
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
Radiology, Nuclear Medicine & Medical Imaging
Kristina Ringe, Annika Bergquist, Henrike Lenzen, Nikolaos Kartalis, Michael P. Manns, Frank Wacker, Aristeidis Grigoriadis
EUROPEAN JOURNAL OF RADIOLOGY
(2020)
Article
Gastroenterology & Hepatology
Gideon M. Hirschfield, Ulrich Beuers, Limas Kupcinskas, Peter Ott, Annika Bergquist, Martti Faerkkilae, Michael P. Manns, Albert Pares, Ulrich Spengler, Michael Stiess, Roland Greinwald, Markus Prols, Dominique Wendum, Uta Drebber, Raoul Poupon
Summary: Budesonide did not improve liver histology in patients with PBC who had insufficient response to UDCA, but demonstrated significant improvements in biochemical markers of disease activity.
JOURNAL OF HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Amandeep Kaur Dhillon, Christian Rupp, Annika Bergquist, Robert Voitl, Trine Folseraas, Marius Troseid, Oivind Midttun, Per M. Ueland, Tom H. Karlsen, Mette Vesterhus, Martin Kummen, Johannes R. Hov
Summary: The study found that levels of neopterin and KT-ratio were elevated in patients with primary sclerosing cholangitis (PSC) and were associated with liver transplantation-free survival in two independent PSC cohorts. However, the lack of association in one cohort reduces the potential clinical value of these biomarkers, highlighting the importance of validating new biomarkers in PSC across multiple cohorts.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Cell Biology
Xiaojun Jiang, Annika Bergquist, Britt-Sabina Loscher, Geetha Venkatesh, Jeff E. Mold, Kristian Holm, Jon K. Laerdahl, Sigrid S. Skanland, Kimia T. Maleki, Martin Cornillet, Kjetil Tasken, Andre Franke, Tom H. Karlsen, Niklas K. Bjorkstrom, Espen Melum
Summary: A heterozygous germline missense mutation in the CD100 gene was found in a family with PSC, leading to T cell functional defects and increased proliferation as well as impaired interferon-gamma production. Mice with homologous mutation showed a higher susceptibility to develop severe cholangitis, which could be attenuated by transferring wild-type T cells. The study suggests a potential therapeutic role for T cells in protecting against PSC.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Hannes Jansson, Pim B. Olthof, Annika Bergquist, Marjolein A. P. Ligthart, Silvio Nadalin, Roberto Troisi, Bas Groot Koerkamp, Ruslan Alikhanov, Hauke Lang, Alfredo Guglielmi, Matteo Cescon, William R. Jarnagin, Luca Aldrighetti, Thomas M. van Gulik, Ernesto Sparrelid
Summary: This study found that the overall survival rate after resection was similar between patients with PSC-associated pCCA and non-PSC patients, but postoperative complications were more frequent in PSC patients.
Review
Genetics & Heredity
A. Waldthaler, C. Schramm, A. Bergquist
Summary: PSC is a rare liver disease that causes biliary strictures and neoplastic development, with ERCP being the primary management strategy.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Aristeidis Grigoriadis, Kristina I. Ringe, Mats Andersson, Nikolaos Kartalis, Annika Bergquist
Summary: The study evaluated the interreader agreement and prognostic performance of two ANALI-scores for patients with PSC, finding poor to moderate agreement and better outcome-free survival rates for patients with low ANALI-scores.
EUROPEAN JOURNAL OF RADIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Hege Marie Vedeld, Marit M. Grimsrud, Kim Andresen, Heidi D. Pharo, Erik von Seth, Tom H. Karlsen, Hilde Honne, Vemund Paulsen, Martti A. Farkkila, Annika Bergquist, Marine Jeanmougin, Lars Aabakken, Kirsten M. Boberg, Trine Folseraas, Guro E. Lind
Summary: The study aimed to establish robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Using ddPCR analysis, high accuracy was achieved in detecting CCA in PSC patients, even up to 12 months before official diagnosis, indicating the potential of these biomarkers to complement current detection methods.
Article
Gastroenterology & Hepatology
Aiva Lundberg Bave, Annika Bergquist, Matteo Bottai, Anna Warnqvist, Erik von Seth, Caroline Nordenvall
Summary: The study found that PSC patients have a four times overall increased risk of developing cancer compared to the general population, with a particularly higher risk of developing hepatobiliary, colorectal, and pancreatic cancer.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Cell Biology
Christine L. Zimmer, Erik von Seth, Marcus Buggert, Otto Strauss, Laura Hertwig, Son Nguyen, Alicia Y. W. Wong, Chiara Zotter, Lena Berglin, Jakob Michaelsson, Marcus Reuterwall Hansson, Urban Arnelo, Ernesto Sparrelid, Ewa C. S. Ellis, Johan D. Soderholm, Asa Keita, Kristian Holm, Volkan Ozenci, Johannes R. Hov, Jeff E. Mold, Martin Cornillet, Andrea Ponzetta, Annika Bergquist, Niklas K. Bjorkstrom
Summary: The study on patients with primary sclerosing cholangitis (PSC) revealed the characteristics of the human biliary immunological landscape, highlighting differences in immune cell composition compared to blood and the pathological features of biliary inflammation in PSC patients.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Christine L. Zimmer, Iva Filipovic, Martin Cornillet, Colm J. O'Rourke, Lena Berglin, Hannes Jansson, Dan Sun, Otto Strauss, Laura Hertwig, Helene Johansson, Erik Seth, Ernesto Sparrelid, Joana Dias, Hans Glaumann, Espen Melum, Ewa C. Ellis, Johan K. Sandberg, Jesper B. Andersen, Annika Bergquist, Niklas K. Bjorkstrom
Summary: The study found that MAIT cells were heterogenously lost from intrahepatic and perihilar cholangiocarcinoma tumors possibly in response to increased bacterial burden, while the residual intratumoral MAIT cells exhibited preserved receptor repertoire for interaction with tumor cells. The high presence of MAIT cells in the livers of iCCA patients predicted long-term survival and was associated with a favorable antitumor immune signature.
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
Oncology
Rithva Rahman, Jonas F. Ludvigsson, Erik von Seth, Jesper Lagergren, Annika Bergquist, Cecilia Radkiewicz
Summary: The incidence of intrahepatic and perihilar cholangiocarcinoma is increasing in Sweden, especially among younger adults, while the incidence of gallbladder cancer is decreasing.
EUROPEAN JOURNAL OF CANCER
(2022)
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
Peder Rustoen Braadland, Kai Markus Schneider, Annika Bergquist, Antonio Molinaro, Anita Lovgren-Sandblom, Marcus Henricsson, Tom Hemming Karlsen, Mette Vesterhus, Christian Trautwein, Johannes Roksund Hov, Hanns-Ulrich Marschall
Summary: The synthesis of bile acids in PSC patients is associated with therapeutic efficacy, and reduced bile acid synthesis is associated with decreased liver transplantation-free survival. In some patients, bile acid synthesis may be fully suppressed, making further pharmacological intervention futile.
