Article
Cell Biology
Theinmozhi Arulraj, Sebastian C. Binder, Michael Meyer-Hermann
Summary: Germinal centers (GCs) are transient structures in secondary lymphoid organs where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. Individual GCs may have varying lifetimes due to factors like antigen availability and founder cell composition, impacting overall GC responses in a primary immune response.
Article
Gastroenterology & Hepatology
Julian Hercun, Mazen Noureddin, Nabil Noureddin, Jason Eccleston, Daniel Woolridge, T. Jake Liang, Michele Tana, David E. Kleiner, Gracia Viana Rodriguez, Christopher Koh, Jay H. Hoofnagle, Theo Heller
Summary: This study evaluated the involvement of bile duct and disease progression in patients with primary biliary cholangitis (PBC) and found that bile duct injury does not follow the same course as fibrosis, and certain indicators are associated with ductopenia progression.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Debashis Haldar, Ashnila Janmohamed, Tim Plant, Matthew Davidson, Hannah Norman, Emily Russell, Olivia Serevina, Kenneth Chung, Kashif Qamar, Bridget Gunson, Bettina Hansen, Alex Richter, Palak J. Trivedi, Gideon M. Hirschfield
Summary: In patients with PBC, the presence of anti-gp210 autoantibodies is associated with adverse clinical manifestations, predicts treatment non-response, and independently predicts decreased transplant-free survival.
LIVER INTERNATIONAL
(2021)
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
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
Thomas W. Warnes, Stephen A. Roberts, Alexander Smith, Victor M. Cope, Patricia Vales, Raymond McMahon
Summary: This study found that measurement of baseline portal pressure is of significant prognostic value in primary biliary cholangitis, providing additional predictive information beyond Mayo score and Ludwig stage.
LIVER INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Xi Li, Yan Li, Jintao Xiao, Huiwen Wang, Yan Guo, Xiuru Mao, Pan Shi, Yanliang Hou, Xiaoxun Zhang, Nan Zhao, Minghua Zheng, Yonghong He, Jingjing Ding, Ya Tan, Min Liao, Ling Li, Ying Peng, Xuan Li, Qiong Pan, Qiaoling Xie, Qiao Li, Jianwei Li, Ying Li, Zhe Chen, Yongxiu Huang, David N. Assis, Shi-Ying Cai, James L. Boyer, Xuequan Huang, Can-E Tang, Xiaowei Liu, Shifang Peng, Jin Chai
Summary: The numbers of DUOX2(+)ACE2(+) small cholangiocytes are inversely associated with disease severity in PBC. They may be the target of pIgR-mediated humoral responses. Protecting these cells and targeting anti-pIgR autoantibodies could be valuable strategies for therapeutic interventions in PBC.
NATURE COMMUNICATIONS
(2023)
Article
Pediatrics
Chenyu Yang, Huiwu Xing, Bingqian Tan, Mingman Zhang
Summary: This study utilized liver tissue sequencing data to predict immune cell infiltration in BA, revealing differentially expressed immune genes related to MHC protein complex, cytokine, chemokine activity, and MHC-II receptor activity. The DE-IGs were found to be mainly enriched in various immune pathways, providing new insights into understanding the pathogenesis of BA.
FRONTIERS IN PEDIATRICS
(2022)
Article
Gastroenterology & Hepatology
Surain B. Roberts, Gideon M. Hirschfield, Lawrence J. Worobetz, Catherine Vincent, Jennifer A. Flemming, Angela Cheung, Karim Qumosani, Mark Swain, Dusanka Grbic, Hin Hin Ko, Kevork Peltekian, Nazia Selzner, Lusine Abrahamyan, Bishoi Aziz, Ellina Lytvyak, Kattleya Tirona, Aliya F. Gulamhusein, Harry L. A. Janssen, Aldo J. Montano-Loza, Andrew L. Mason, Bettina E. Hansen
Summary: In a diverse Canadian cohort of PBC patients, Indigenous Canadians have poorer liver transplant-free and event-free survival compared to White patients. They are more likely to have a clinical event before diagnosis and present with higher liver function test indicators, which persist during follow-up.
Review
Oncology
Stefania De Lorenzo, Francesco Tovoli, Franco Trevisani
Summary: This review provides important information on the mechanisms and therapeutic strategies for immune checkpoint inhibitor (ICI) resistance in hepatocellular carcinoma (HCC), aiming to guide clinicians and researchers.
Article
Gastroenterology & Hepatology
Ben Barron-Millar, Laura Ogle, George Mells, Steven Flack, Jonathan Badrock, Richard Sandford, John Kirby, Jeremy Palmer, Laura Jopson, John Brain, Graham R. Smith, Steve Rushton, Vinod S. Hegade, Rebecca Jones, Simon Rushbrook, Douglas Thorburn, Steve Ryder, Gideon Hirschfield, Jessica K. Dyson, David E. J. Jones
Summary: The UK-PBC study aimed to explore the biological basis of UDCA nonresponse in primary biliary cholangitis (PBC) and identified a set of serum chemokines potentially related to cellular senescence with significant differential expression between responders and nonresponders. These proteins have the potential to serve as biomarkers for high-risk disease identification and should be further evaluated for their clinical utility in prospective studies.
Article
Genetics & Heredity
Bin Ke, Chunyu Li, Huifang Shang
Summary: Hematologic abnormalities are associated with the susceptibility of primary biliary cholangitis (PBC), but whether there is a causal association is still unclear. In this study, we conducted analyses to explore the causative role of hematological traits in the risk of PBC. The results showed that genetically higher hemoglobin and hematocrit levels are associated with a reduced risk of PBC, providing potential targets for disease prevention and treatment.
JOURNAL OF HUMAN GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Ludovico Abenavoli, Giuseppe Guido Maria Scarlata, Maria Rosaria Paravati, Luigi Boccuto, Francesco Luzza, Emidio Scarpellini
Summary: Liver transplantation is the preferred treatment for patients with certain liver conditions, but rejection after transplantation is a significant issue. The gut microbiota is involved in the gut-liver axis and can affect the immune response, potentially leading to graft rejection. Evaluating changes in the gut microbiota composition is essential for monitoring the success of liver transplantation and implementing appropriate preventive measures.
Article
Cell Biology
Giulia Jannone, Eliano Bonaccorsi Riani, Catherine de Magnee, Roberto Tambucci, Jonathan Evraerts, Joachim Ravau, Pamela Baldin, Caroline Bouzin, Axelle Loriot, Laurent Gatto, Anabelle Decottignies, Mustapha Najimi, Etienne Marc Sokal
Summary: Premature senescence occurs in patients with biliary atresia, leading to liver dysfunction. Treatment with liver-derived progenitor cells can reduce senescence and improve liver disease.
Review
Gastroenterology & Hepatology
Palak J. Trivedi, Stefan G. Hubscher, Michael Heneghan, Dermot Gleeson, Gideon M. Hirschfield
JOURNAL OF HEPATOLOGY
(2019)
Editorial Material
Medicine, General & Internal
Evaggelia Liaskou, Gideon M. Hirschfield
Editorial Material
Gastroenterology & Hepatology
Maya Deeb, Tom H. Karlsen, Gideon M. Hirschfield
JOURNAL OF HEPATOLOGY
(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)
Editorial Material
Gastroenterology & Hepatology
Surain B. Roberts, Amol A. Verma, Gideon M. Hirschfield
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Gastroenterology & Hepatology
Surain B. Roberts, Bettina E. Hansen, Saeha Shin, Lusine Abrahamyan, Lauren Lapointe-Shaw, Harry L. A. Janssen, Fahad Razak, Amol A. Verma, Gideon M. Hirschfield
Summary: Liver disease is a growing burden on population health globally, with liver disease patients in Toronto-area hospitals having higher mortality rates and resource use compared to common cardio-respiratory conditions such as heart failure, COPD, and pneumonia. Re-evaluation of approaches to caring for inpatients with liver disease is necessary.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Gastroenterology & Hepatology
Palak J. Trivedi, Gideon M. Hirschfield
Summary: Autoimmune liver diseases, including primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis, show meaningful changes in disease epidemiology with increasing incidence and prevalence in Europe, North America, and the Asia-Pacific region. Global variations exist in contemporary incidence rates, with age, sex, and race impacting clinical outcomes and the need for gastroenterology, hepatology, and organ transplant services.
Article
Gastroenterology & Hepatology
Kristel K. Leung, Audrey Kim, Bettina E. Hansen, Les Lilly, Nazia Selzner, Keyur Patel, Mamatha Bhat, Gideon M. Hirschfield, Zita Galvin
Summary: This study analyzed the impact of organ allocation in liver transplantation, finding that patient social determinants and primary liver disease etiology continue to be significantly associated with ultimate transplantation.
LIVER TRANSPLANTATION
(2021)
Article
Gastroenterology & Hepatology
Aldo J. Montano-Loza, Vincenzo Ronca, Maryam Ebadi, Bettina E. Hansen, Gideon Hirschfield, Saleh Elwir, Mohamad Alsaed, Piotr Milkiewicz, Maciej K. Janik, Hanns-Ulrich Marschall, Maria Antonella Burza, Cumali Efe, Ali Riza Caliskan, Murat Harputluoglu, Gokhan Kabacam, Debora Terrabuio, Fernanda de Quadros Onofrio, Nazia Selzner, Alan Bonder, Albert Pares, Laura Llovet, Murat Akyildiz, Cigdem Arikan, Michael P. Manns, Richard Taubert, Anna-Lena Weber, Thomas D. Schiano, Brandy Haydel, Piotr Czubkowski, Piotr Socha, Natalia Oldak, Nobuhisa Akamatsu, Atsushi Tanaka, Cynthia Levy, Eric F. Martin, Aparna Goel, Mai Sedki, Irena Jankowska, Toru Ikegami, Maria Rodriguez, Martina Sterneck, Christina Weiler-Normann, Christoph Schramm, Maria Francesca Donato, Ansgar Lohse, Raul J. Andrade, Vilas R. Patwardhan, Bart van Hoek, Maaike Biewenga, Andreas E. Kremer, Yoshihide Ueda, Mark Deneau, Mark Pedersen, Marlyn J. Mayo, Annarosa Floreani, Patrizia Burra, Maria Francesca Secchi, Benedetta Terziroli Beretta-Piccoli, Marco Sciveres, Giuseppe Maggiore, Syed-Mohammed Jafri, Dominique Debray, Muriel Girard, Florence Lacaille, Ellina Lytvyak, Andrew L. Mason, Michael Heneghan, Ye Htun Oo
Summary: Recurrence of autoimmune hepatitis (AIH) is common after liver transplantation, and it is associated with younger age at transplantation, the use of mycophenolate mofetil post-transplant, sex mismatch, and high pre-transplant IgG levels. Recurrent AIH is associated with impaired graft and overall survival. Better characterization, prevention, and treatment strategies are needed for the management of recurrent AIH.
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Christopher L. Bowlus, Michael R. Galambos, Richard J. Aspinall, Gideon M. Hirschfield, David E. J. Jones, Yvonne Doerffel, Stuart C. Gordon, Stephen A. Harrison, Andreas E. Kremer, Marlyn J. Mayo, Paul J. Thuluvath, Cynthia Levy, Mark G. Swain, Guy W. Neff, David A. Sheridan, Carmen M. Stanca, Christoph P. Berg, Aparna Goel, Mitchell L. Shiffman, John M. Vierling, Pol Boudes, Alexandra Steinberg, Yun-Jung Choi, Charles A. McWherter
Summary: This study examined the efficacy and safety of seladelpar in patients with primary biliary cholangitis (PBC). The results showed that seladelpar significantly improved biochemical markers of cholestasis and inflammation, and the improvements were maintained or improved after dose escalation at 52 weeks. The treatment was safe and not associated with worsening pruritus.
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Gideon M. Hirschfield, Mitchell L. Shiffman, Aliya Gulamhusein, Kris Kowdley, John M. Vierling, Cynthia Levy, Andreas E. Kremer, Ehud Zigmond, Pietro Andreone, Stuart C. Gordon, Christopher L. Bowlus, Eric J. Lawitz, Richard J. Aspinall, Daniel S. Pratt, Karina Raikhelson, Maria S. Gonzalez-Huezo, Michael A. Heneghan, Sook-Hyang Jeong, Alma L. Ladron de Guevara, Marlyn J. Mayo, George N. Dalekos, Joost P. H. Drenth, Ewa Janczewska, Barbara A. Leggett, Frederik Nevens, Victor Vargas, Eli Zuckerman, Christophe Corpechot, Eduardo Fassio, Holger Hinrichsen, Pietro Invernizzi, Palak J. Trivedi, Lisa Forman, David E. J. Jones, Stephen D. Ryder, Mark G. Swain, Alexandra Steinberg, Pol F. Boudes, Yun-Jung Choi, Charles A. McWherter
Summary: This study evaluated the efficacy and safety of seladelpar in patients with primary biliary cholangitis who had inadequate response or intolerance to ursodeoxycholic acid. The results showed that seladelpar significantly improved liver biochemistry and pruritus in these patients, and it was well tolerated.
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
Laura Martinez-Gili, Alexandros Pechlivanis, Julie A. K. McDonald, Sofina Begum, Jonathan Badrock, Jessica K. Dyson, Rebecca Jones, Gideon Hirschfield, Stephen D. Ryder, Richard Sandford, Simon Rushbrook, Douglas Thorburn, Simon D. Taylor-Robinson, Mary M. E. Crossey, Julian R. Marchesi, George Mells, Elaine Holmes, David Jones
Summary: A study on patients with primary biliary cholangitis (PBC) showed that there is variation in response to ursodeoxycholic acid (UDCA) treatment. Responders exhibited high levels of secondary and tertiary bile acids, while non-responders had lower urinary bile acid levels and higher levels of 12-dehydrocholic acid. Additionally, non-responders showed lower gut microbiota diversity and lower capacity for bile acid deconjugation.
Review
Medicine, General & Internal
Georg Beyer, Aida Habtezion, Jens Werner, Markus M. Lerch, Julia Mayerle
Review
Gastroenterology & Hepatology
Kristel K. Leung, Maya Deeb, Gideon M. Hirschfield
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2020)
