Article
Cell Biology
Laura M. Molina, Junjie Zhu, Qin Li, Tirthadipa Pradhan-Sundd, Yekaterina Krutsenko, Khaled Sayed, Nathaniel Jenkins, Ravi Vats, Bharat Bhushan, Sungjin Ko, Shikai Hu, Minakshi Poddar, Sucha Singh, Junyan Tao, Prithu Sundd, Aatur Singhi, Simon Watkins, Xiaochao Ma, Panayiotis Benos, Andrew Feranchak, George Michalopoulos, Kari Nejak-Bowen, Alan Watson, Aaron Bell, Satdarshan P. Monga
Summary: YAP1 plays a key role in bile duct development, while hepatocytes achieve adaptation through reduced metabolic and synthetic function to survive for 8 months, blocking the formation of the biliary tree.
Article
Endocrinology & Metabolism
Shengnan Zhou, Weijie Chen, Xuesong Bai, Jiemin Chen, Qiang Xu, Liangbo Dong, Wei Chen, Qiang Qu, Xiaodong He
Summary: This study found that hypothalamic POMC neurons were upregulated after biliary diversion, and increased taurocholic acid (TCA), taurodeoxycholic acid (TDCA), and the gut-derived hormone FGF15 may activate POMC neurons.
FRONTIERS IN ENDOCRINOLOGY
(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
Radiology, Nuclear Medicine & Medical Imaging
Hassan Aboughalia, Helen H. R. Kim, Andre A. S. Dick, M. Cristina Pacheco, Robert E. Cilley, Ramesh S. Iyer
Summary: This paper discusses the spectrum of pathologies affecting the pediatric biliary tree, imaging modalities used for assessment, and unique features of pediatric biliary pathologies, emphasizing the importance of understanding the imaging features of biliary pathologies for clinical management.
Review
Pharmacology & Pharmacy
Phillip Sanchez, Atena Farkhondeh, Ivan Pavlinov, Karsten Baumgaertel, Steven Rodems, Wei Zheng
Summary: Advancements in treating the rare genetic disorder known as Alagille Syndrome (ALGS) have been slow due to the variety of mutations in the JAG1 and NOTCH2 genes. Current treatment plans focus on relieving symptoms rather than addressing the underlying causes of the disease. Developing targeted therapies for ALGS is challenging due to the central role of the Notch signaling pathway in cancer.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Medicine, General & Internal
Hafiza Sidra Tul Muntaha, Mubashar Munir, Syeda Haleema Sajid, Zouina Sarfraz, Azza Sarfraz, Karla Robles-Velasco, Muzna Sarfraz, Miguel Felix, Ivan Cherrez-Ojeda
Summary: This study provides the latest evidence for the efficacy of ileal bile acid transport (IBAT) blockers in patients with Alagille syndrome (ALGS). The results demonstrate that these drugs can significantly reduce itch and serum bile acid levels, while improving fatigue and quality of life. However, these drugs may lead to elevated levels of alanine aminotransferase (ALT).
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Gastroenterology & Hepatology
Samar H. Ibrahim, Binita M. Kamath, Kathleen M. Loomes, Saul J. Karpen
Summary: With the application of modern investigative technologies, more genetic cholestatic liver diseases are being identified as the root cause of previously labeled idiopathic adult and pediatric liver diseases. Risk stratification based on the severity of genetic defects can guide treatment decisions, while recently approved therapies show promise in helping patients with genetic causes of cholestasis.
Review
Oncology
Giovanni Vitale, Alessandro Mattiaccio, Amalia Conti, Laura Turco, Marco Seri, Fabio Piscaglia, Maria Cristina Morelli
Summary: This review summarizes the relationship between inherited cholestasis, bile acids, gut microbiota, and the risk of hepatobiliary tumors. It discusses specific genetic pathways and their role in cholestasis and hepatobiliary tumors, as well as the impact of mutations in FIC genes on bile acid levels. Experimental studies have shown that high bile acid concentrations can lead to inflammation, apoptosis resistance, and increased cell regeneration, which are all risk factors for hepatocellular carcinoma and cholangiocarcinoma.
Article
Biochemistry & Molecular Biology
Lukasz Krupa, Robert Staron, Dorota Dulko, Natalia Lozinska, Alan R. Mackie, Neil M. Rigby, Adam Macierzanka, Aleksandra Markiewicz, Christian Jungnickel
Summary: The study determined that serum bilirubin is a good indicator of the type of biliary obstruction, able to differentiate between benign obstructions such as choledocholithiasis and malignant changes such as pancreatic neoplasms or cholangiocarcinoma. Additionally, it was shown that conjugated/unconjugated bile salts confirm the presence of an obstruction, with lower levels indicating increased possibilities of inflammation and neoplasms.
Article
Surgery
Jonathan M. Durgin, Robert Crum, Heung Bae Kim, Alex G. Cuenca
Summary: Alagille syndrome is a disorder characterized by increased cholesterol and bile acids in the blood, leading to debilitating xanthomas and pruritus. This study found that Roux-en-Y cholecystocolostomy can be an effective treatment for AGS that is refractory to medical management.
JOURNAL OF SURGICAL CASE REPORTS
(2022)
Article
Immunology
Ru Feng, Tianyu Zhang, Masood Ur Rehman Kayani, Zhengting Wang, Yao Shen, Kenn Liu Su, Kouken Bielike, Lei Chen
Summary: The bacterial family Alcaligenaceae increase in relative abundance in lithiasis group compared with non-lithiasis group. PBDS group shows significantly lower bacterial diversity than SBDS, with certain significant bacteria families decreased in relative abundance. wMGS reveals increased ability of biofilm synthesis and ability to sense external stimuli in PBDS.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Pediatrics
Masahiro Takeda, Seisuke Sakamoto, Hajime Uchida, Seiichi Shimizu, Yusuke Yanagi, Akinari Fukuda, Takako Yoshioka, Mureo Kasahara
Summary: By validating the morphological and histopathological features in detail, it may help differentiate between Alagille syndrome with extrahepatic bile duct obstruction and biliary atresia.
PEDIATRIC SURGERY INTERNATIONAL
(2021)
Article
Surgery
Abdulla Sahloul, Elke Lainka, Simone Kathemann, Sandra Swoboda, Carola Droege, Verena Keitel, Yahya Saleh Al-Matary, Michael Berger, Maren Schulze
Summary: In our retrospective analysis, we found that biliary diversion effectively reduced bile acids, cholesterol levels, and triglycerides in children with PFIC 1, but not in those with PFIC 2. Furthermore, a decrease in bile acids following biliary diversion predicted the need for liver transplantation.
FRONTIERS IN SURGERY
(2023)
Article
Gastroenterology & Hepatology
Jens Mittler, Kenneth D. Chavin, Stefan Heinrich, Roman Kloeckner, Tim Zimmermann, Hauke Lang
Summary: This study demonstrated the feasibility and success of duct-to-duct biliary reconstruction in selected patients requiring surgical repair for isolated AS after DDLT. Patients who underwent this procedure had fully normalized liver function tests post-operatively and did not require any biliary interventions. Although there were cases of post-operative complications such as intraoperative cholangiosepsis and subhepatic abscess, there were no perioperative deaths.
JOURNAL OF GASTROINTESTINAL SURGERY
(2021)
Review
Gastroenterology & Hepatology
Alvin P. Chan, Robert S. Venick
Summary: Thanks to innovations in medical and surgical therapies, children with cholestatic liver diseases are living longer. Pediatric liver transplantation, especially for biliary atresia, has greatly improved outcomes. Molecular genetic testing has sped up diagnosis for other cholestatic disorders, aiding in management, prognosis, and family planning. Therapeutics like bile acids and bile acid transport inhibitors have slowed disease progression and improved quality of life for certain disorders. The aim of this review is to bridge the gap between pediatric and adult care for these childhood cholestatic liver diseases.
JOURNAL OF CLINICAL GASTROENTEROLOGY
(2023)
Letter
Gastroenterology & Hepatology
Tassos Grammatikopoulos, Richard J. Thompson
JOURNAL OF HEPATOLOGY
(2017)
Editorial Material
Gastroenterology & Hepatology
Richard J. Thompson
JOURNAL OF HEPATOLOGY
(2017)
Article
Gastroenterology & Hepatology
Sze Pheh Yeap, Hugh Harley, Richard Thompson, Kate Diana Williamson, John Bate, Farah Sethna, Geoffrey Farrell, William Bill Hague
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2019)
Article
Pediatrics
Tassos Grammatikopoulos, Maesha Deheragoda, Sandra Strautnieks, Lara Neves Souza, Rupert Hinds, Richard J. Thompson, Nedim Hadzic
JOURNAL OF PEDIATRICS
(2018)
Article
Gastroenterology & Hepatology
Laura N. Bull, Richard J. Thompson
CLINICS IN LIVER DISEASE
(2018)
Article
Gastroenterology & Hepatology
John-Paul Berauer, Anya I. Mezina, David T. Okou, Aniko Sabo, Donna M. Muzny, Richard A. Gibbs, Madhuri R. Hegde, Pankaj Chopra, David J. Cutler, David H. Perlmutter, Laura N. Bull, Richard J. Thompson, Kathleen M. Loomes, Nancy B. Spinner, Ramakrishnan Rajagopalan, Stephen L. Guthery, Barry Moore, Mark Yandell, Sanjiv Harpavat, John C. Magee, Binita M. Kamath, Jean P. Molleston, Jorge A. Bezerra, Karen F. Murray, Estella M. Alonso, Philip Rosenthal, Robert H. Squires, Kasper S. Wang, Milton J. Finegold, Pierre Russo, Averell H. Sherker, Ronald J. Sokol, Saul J. Karpen
Article
Gastroenterology & Hepatology
Maria Pires, James Underhill, Abdel Douiri, Alberto Quaglia, Wayel Jassem, William Bernal, Nigel Heaton, Phillip Morgan, Richard Thompson, J. Michael Tredger
Summary: Complement C3 genotype may influence patient and graft outcomes after liver transplantation, with the donor C3 F variant particularly impacting liver graft survival and the recipient C3 genotype potentially affecting graft survival. However, C3 genotype does not independently determine rejection incidence. Additionally, the type of liver donor (circulatory-death vs. brain-death) may also play a role in rejection incidence.
INTERNATIONAL JOURNAL OF HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Jeremy S. Nayagam, Rebecca Jeyaraj, Pierre Foskett, Anil Dhawan, Aftab Ala, Deepak Joshi, Adrian Bomford, Richard J. Thompson
Summary: This study retrospectively reviewed 117 patients with hepatic Wilson disease, and found that patients with LOF variants in the ATP7B gene have a worse prognosis during long-term treatment. Close monitoring is recommended for this subgroup of patients to ensure early detection and management of disease progression.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Richard J. Thompson, Henrik Arnell, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Ozlem Durmaz, Bjorn Fischler, Emmanuel Gonzales, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H. J. Houwen, Binita M. Kamath, Saul J. Karpen, Lise Kjems, Florence Lacaille, Alain Lachaux, Elke Lainka, Cara L. Mack, Jan P. Mattsson, Patrick McKiernan, Hasan Ozen, Sanjay R. Rajwal, Bertrand Roquelaure, Mohammad Shagrani, Eyal Shteyer, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Henkjan J. Verkade, Patrick Horn
Summary: The study evaluated the effects of odevixibat, an ileal bile acid transporter inhibitor, versus placebo in children with PFIC. The results showed that odevixibat effectively reduced pruritus and serum bile acids compared to placebo, and it was generally well-tolerated.
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Ronald J. Sokol, Emmanuel M. Gonzales, Binita M. Kamath, Alastair Baker, Pamela Vig, Douglas B. Mogul, Will Garner, Bettina E. Hansen, Emmanuel Jacquemin, Richard J. Thompson
Summary: Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events in patients with Alagille syndrome (ALGS) treated with maralixibat (MRX).
Editorial Material
Gastroenterology & Hepatology
Richard J. Thompson
Article
Gastroenterology & Hepatology
Antonia Felzen, Daan B. E. van Wessel, Emmanuel Gonzales, Richard J. Thompson, Irena Jankowska, Benjamin L. Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipinski, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Bjoern Fischler, Jan B. F. Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Munoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsofi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy J. van der Woerd, Binita M. Kamath, Jian-She Wang, Liting Li, Ozlem Durmaz, Nanda Kerkar, Marianne Horby Jorgensen, Ryan Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Cristina Targa Ferreira, Felipe Ordonez Guerrero, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa de Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Aglaia Zellos, Estella M. Alonso, Ronald J. Sokol, Frederick J. Suchy, Kathleen M. Loomes, Patrick J. McKiernan, Philip Rosenthal, Yumirle Turmelle, Simon Horslen, Kathleen Schwarz, Jorge A. Bezerra, Kasper Wang, Bettina E. Hansen, Henkjan J. Verkade
Summary: This study aimed to evaluate the relationship between genetic mutations related to BSEP deficiency and clinical features. The results showed that the combination of one relatively mild mutation and one severe mutation resulted in a clinical presentation similar to patients with two severe mutations, and they had a poor response to surgical interruption of the enterohepatic circulation.
Article
Gastroenterology & Hepatology
Richard J. Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Ozlem Durmaz, Emmanuel Gonzales, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H. J. Houwen, Binita M. Kamath, Saul J. Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M. Loomes, Cara L. Mack, Jan P. Mattsson, Patrick Mckiernan, Quanhong Ni, Hasan Ozen, Sanjay R. Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J. Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L. van der Woerd, Henkjan J. Verkade, Jennifer M. Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, Lise Kjems
Summary: The ongoing PEDFIC 2 study evaluated the effectiveness of odevixibat in patients with progressive familial intrahepatic cholestasis. The study found that odevixibat can reduce serum bile acids and alleviate pruritus symptoms. This suggests that odevixibat may be a safe and effective treatment option for patients with progressive familial intrahepatic cholestasis.
Article
Gastroenterology & Hepatology
Jeremy S. Nayagam, Pierre Foskett, Sandra Strautnieks, Kosh Agarwal, Rosa Miquel, Deepak Joshi, Richard J. Thompson
Summary: This study aims to investigate the variants in ATP8B1, ABCB11, and ABCB4 genes in adult-onset liver disease patients and explore the correlation between genotype and phenotype. The results show that these variants are frequently identified in patients with cholestasis and are likely to contribute to the development of liver disease. ABCB4 and ABCB11 variants are associated with chronic liver disease and pregnancy-associated liver dysfunction.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Laura N. Bull, Ludmila Pawlikowska, Sandra Strautnieks, Irena Jankowska, Piotr Czubkowski, Jennifer L. Dodge, Karan Emerick, Catherine Wanty, Sami Wali, Samra Blanchard, Florence Lacaille, Jane A. Byrne, Albertien M. van Eerde, Kaija-Leena Kolho, Roderick Houwen, Steven Lobritto, Vera Hupertz, Patricia McClean, Giorgina Mieli-Vergani, Etienne Sokal, Philip Rosenthal, Peter F. Whitington, Joanna Pawlowska, Richard J. Thompson
HEPATOLOGY COMMUNICATIONS
(2018)
