Review
Biochemistry & Molecular Biology
Annarosa Floreani, Daniela Gabbia, Sara De Martin
Summary: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with limited treatment options. Ursodeoxycholic acid (UDCA) is the first-line therapy but is ineffective for a significant portion of patients. Obeticholic acid (OCA) is an effective second-line treatment for UDCA-non responders. Future therapies for PBC are promising.
Review
Biochemistry & Molecular Biology
Annarosa Floreani, Daniela Gabbia, Sara De Martin
Summary: Ursodeoxycholic acid is the first-line therapy for PBC, but new pharmacological agents are being proposed for UDCA-non-responders. Obeticholic acid and fibrates have shown effectiveness in improving biochemistry alteration and symptoms of PBC. Other new agents with different mechanisms of action are also under clinical evaluation for PBC treatment.
Review
Gastroenterology & Hepatology
Kris. V. V. Kowdley, Christopher. L. L. Bowlus, Cynthia Levy, Marlyn. J. J. Mayo, Daniel. S. S. Pratt, Raj Vuppalanchi, Zobair. M. M. Younossi
Summary: Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease. There have been recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. In this updated expert consensus document, we provide updates on staging, noninvasive prognostic tools, and a treatment algorithm for clinicians managing PBC.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Gastroenterology & Hepatology
David Jones, Marco Carbone, Pietro Invernizzi, Nicola Little, Frederik Nevens, Mark G. Swain, Philippe Wiesel, Cynthia Levy
Summary: This post hoc analysis evaluated the potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life in primary biliary cholangitis (PBC). The results showed that patients treated with setanaxib experienced significant reduction in fatigue scores, especially in those with moderate-to-severe fatigue, and this improvement was correlated with emotional, social, symptom, and cognitive improvements.
HEPATOLOGY COMMUNICATIONS
(2023)
Review
Gastroenterology & Hepatology
Albert Pares
Summary: Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease predominantly affecting middle-aged women. Despite standard treatment, many patients have an inadequate response and require second-line therapy. This article reviews the main characteristics of PBC and provides a practical algorithm for diagnosis and management.
REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS
(2022)
Article
Gastroenterology & Hepatology
Kazuhito Kawata, Satoru Joshita, Shinji Shimoda, Yuki Yamashita, Maho Yamashita, Kensuke Kitsugi, Shingo Takatori, Kazuyoshi Ohta, Jun Ito, Shin Shimoyama, Hidenao Noritake, Takafumi Suda, Kenichi Harada
Summary: The URS can predict the biochemical response to UDCA treatment in PBC patients, as well as reflect histopathological features before treatment. This scoring system can identify inadequate histological response to UDCA treatment in the Scheuer classification and the Nakanuma system.
HEPATOLOGY RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Anna Reig, Carmen Alvarez-Navascues, Mercedes Vergara, Elena Gomez-Dominguez, Adolfo Gallego-Moya, Indhira M. Perez-Medrano, Emilio Fabrega, Manuel Hernandez-Guerra, Marina Berenguer, Pamela Estevez, Ana Arencibia, Rosa M. Morillas, Diana Horta, Agustin Albillos, Marta Casado, Gema De la Cruz, Eva Fernandez-Bonilla, Esther Molina, Lander Hijona, Moises Diago, Conrado M. Fernandez-Rodriguez, Jesus M. Gonzalez-Santiago, Margarita Sala, Judith Gomez-Camarero, Manuel Romero-Gomez, Francisco Suarez, Victor Vargas, Carlos Ferre-Aracil, Raul J. Andrade, Nadia Chahri, Albert Pares
Summary: The therapy of OCA and fibrates can improve hepatic biochemistry and the GLOBE score in patients with primary biliary cholangitis, and simultaneous treatment with both can also improve ALP levels.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yun Zhang, Xiaoli Fan, Bin Song, Yifeng Liu, Yidi Chen, Tianying Zheng, Yuxin Guo, Ting Duan, Zixing Huang, Li Yang
Summary: This study explored the feasibility of using nonenhanced magnetic resonance imaging (MRI) to predict insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). The results showed that a predictive model based on three pretreatment MRI features could accurately predict insufficient biochemical response to UDCA treatment in PBC patients within 12 months. Early identification of high-risk patients can facilitate the timely initiation of additional treatment.
EUROPEAN RADIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Nadir Abbas, Emma L. Culver, Douglas Thorburn, Neil Halliday, Hannah Crothers, Jessica K. Dyson, April Phaw, Richard Aspinall, Salim I. Khakoo, Yiannis Kallis, Belinda Smith, Imran Patanwala, Anne McCune, Chenchu R. Chimakurthi, Vinod Hegade, Michael Orrell, Rebecca Jones, George Mells, Colette Thain, Robert-Mitchell Thain, David Jones, Gideon Hirschfield, Palak J. Trivedi
Summary: This study aimed to evaluate the effectiveness of obeticholic acid (OCA) and fibric acid derivatives as second-line treatments for primary biliary cholangitis. The study found that rates of biochemical response and drug discontinuation were similar between fibric acid derivatives and OCA in patients in the United Kingdom.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Medicine, General & Internal
Roshni Patel, Greta Portone, Joshua A. Lambert, Sau Mak, Laith Alrubaiy
Summary: Primary biliary cholangitis is characterized by autoimmune destruction of bile ducts, with gaps in patient care highlighted in publications. Ursodeoxycholic acid is recommended for all patients, with potential disease-modifying therapies like fibrates and budesonide requiring further investigation. Emerging therapies show initial promise but more randomized trials are needed for evaluation.
BRITISH JOURNAL OF HOSPITAL MEDICINE
(2021)
Review
Medicine, General & Internal
Alex Smith, Benjamin Giles, Richard J. Aspinall
Summary: Recent years have witnessed significant progress in our understanding and management of primary biliary cholangitis. Large multicentre studies have provided extensive data on the natural course of the disease, facilitating the identification of high-risk patients and the development of new medications. Recent guidelines underscore the importance of risk stratification, targeted symptom management, and early initiation of second-line therapies.
BRITISH JOURNAL OF HOSPITAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Omar Y. Mousa, Brian D. Juran, Bryan M. McCauley, Mette N. Vesterhus, Trine Folseraas, Coleman T. Turgeon, Ahmad H. Ali, Erik M. Schlicht, Elizabeth J. Atkinson, Chang Hu, Denise Harnois, Elizabeth J. Carey, Andrea A. Gossard, Devin Oglesbee, John E. Eaton, Nicholas F. LaRusso, Gregory J. Gores, Tom H. Karlsen, Konstantinos N. Lazaridis
Summary: In patients with PSC, alterations in plasma BA consistent with cholestasis, UDCA treatment, and IBD were observed. BA profiles were able to predict future hepatic decompensation, demonstrating the clinical potential of BA profiling for use in clinical trials.
Review
Gastroenterology & Hepatology
Abigail Medford, Jonathan Childs, Ashleigh Little, Sanjukta Chakraborty, Leonardo Baiocchi, Gianfranco Alpini, Shannon Glaser
Summary: The liver plays a crucial role in various metabolic and regulatory processes in the body. Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by bile duct inflammation and loss of tolerance to mitochondrial antigens. Ursodeoxycholic acid (UDCA) is currently the first-line treatment for PBC, but additional therapeutics can also be used to manage symptoms and slow disease progression. Liver transplantation is the only potentially curative option for end-stage liver disease or intractable pruritus. This review aims to provide insights into the pathogenesis of PBC and discuss current therapeutic strategies.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Annarosa Floreani, Sara De Martin
Summary: PSC is a chronic cholestatic liver disease with no effective treatment currently available. There is controversy over the use of UDCA in PSC treatment. Novel pharmacological strategies targeting bile composition, immunomodulation, gut microbiome, and fibrosis are emerging, suggesting potential for personalized combination therapies for successful PSC treatment.
DIGESTIVE AND LIVER DISEASE
(2021)
Article
Gastroenterology & Hepatology
Alexander M. Sy, Raphaella D. Ferreira, Binu V. John
Summary: Several studies have shown that patients with PBC have an increased risk of developing HCC. Risk factors for HCC in PBC include advanced age, male sex, comorbidities, and advanced liver fibrosis. The role of treatment response as a risk factor for HCC development in PBC patients should be further investigated. HCC in PBC has a poor prognosis compared to other chronic liver diseases with HCC, and liver transplantation offers the highest survival rate among available therapies.
CLINICS IN LIVER DISEASE
(2022)
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)