Article
Biochemistry & Molecular Biology
Natarajan Balasubramaniyan, Michael W. Devereaux, David J. Orlicky, Ronald J. Sokol, Frederick J. Suchy
Summary: In this study, it was found that miR-199a-5p may contribute to the depletion of ABCB11/Abcb11 in obstructive cholestasis, and the FXR agonist OCA can decrease miR-199a-5p expression. Additionally, NcoR1 may play a role in the regulation of miR-199a-2.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Genetics & Heredity
Emily L. Starke, Keelan Zius, Scott A. Barbee
Summary: Mutations in the KH RNA binding domains of FMRP disrupt the formation of RNA transport granules in neurons, leading to defects in translational repression and localization of target mRNAs.
Article
Medicine, Research & Experimental
Qiong Pan, Gang Luo, Jiaquan Qu, Sheng Chen, Xiaoxun Zhang, Nan Zhao, Jingjing Ding, Hong Yang, Mingqiao Li, Ling Li, Ying Cheng, Xuan Li, Qiaoling Xie, Qiao Li, Xueqian Zhou, Huiling Zou, Shijun Fan, Lingyun Zou, Wei Liu, Guohong Deng, Shi-Ying Cai, James L. Boyer, Jin Chai
Summary: The homozygous mutation of SEMA7A(R145W) leads to intrahepatic cholestasis in both mice and children, with further studies showing that this mutation affects the expression of hepatic bile acid transporters and export pumps.
EMBO MOLECULAR MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Qiuju Tian, Ruiyuan Yang, Yan Wang, Jimin Liu, Aileen Wee, Romil Saxena, Lan Wang, Min Li, Liwei Liu, Shan Shan, Yuanyuan Kong, Hong Ma, Xiaojuan Ou, Hong You, Xinyan Zhao, Jidong Jia
Summary: This study found significant differences in 30 out of 37 bile acids between patients with DILI and healthy controls, with levels of TCA associated with severity and clinical resolution of DILI. ABCB11 gene variants did not impact serum bile acid profiles, DILI severity, or clinical resolution, but reduced BSEP protein expression in liver tissue was associated with altered serum bile acid levels.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Maya Ron, Igor Ulitsky
Summary: The post-transcriptional fate of long RNAs is determined by the specific sequence elements, the splicing status, and the presence of terminal features unique to linear RNAs in a combinatorial manner, which is strongly dependent on the form (linear or circular) and splicing status (spliced or unspliced) of the host RNA.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Paresh P. Chothe, Rachel Pemberton, Niresh Hariparsad
Summary: This study confirmed the transport function and protein abundance of BSEP in SHH, highlighting its major role in bile salt transportation.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Toxicology
Hong Feng, Yan Hu, Shaoyu Zhou, Yuanfu Lu
Summary: Knockout of FXR can alleviate OA-induced cholestatic liver injury in mice by reducing bile acid accumulation in the liver and serum, increasing bile acid export via bile, and upregulating bile acid detoxification enzymes.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Article
Cell Biology
Yoko Sakai, Masanari Matsumura, Takahiro Iwao, Tamihide Matsunaga
Summary: The development of predictive models for hepatotoxicity is necessary due to the undetectable risk in nonclinical studies. Cholestatic drug-induced liver injury (DILI) occurs when bile acids are abnormally excreted and accumulated in hepatocytes, caused by the inhibition of bile salt export pump (BSEP). Human-derived cells are required for accurate assessments, although primary human hepatocytes (PHHs) face challenges in maintaining function and forming bile canaliculi. This study successfully cultured PHHs with optimal conditions, leading to the formation of bile canaliculi and functional BSEP, suggesting improved accuracy in predicting cholestatic DILI-contained toxicity.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2023)
Article
Cell Biology
Shang-Hsin Wu, Mei-Hwei Chang, Ya-Hui Chen, Hui-Lin Wu, Huey-Huey Chua, Chin-Sung Chien, Yen-Hsuan Ni, Hui-Ling Chen, Huey-Ling Chen
Summary: This study identified charged multivesicular body protein 5 (CHMP5) as a molecule that interacts with BSEP, affecting its canalicular targeting and retention, resulting in impaired post-Golgi trafficking and bile acid secretion. These findings suggest that ESCRT-III-mediated BSEP sorting is essential for the trafficking of apical membrane proteins, providing new targets for therapeutic interventions in BSEP-associated cholestasis.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Irena Sliskovic, Hannah Eich, Michaela Muller-McNicoll
Summary: Members of the SR protein family are multifunctional RNA-binding proteins that play key roles in mRNP formation and splicing. In addition to their essential roles in constitutive and alternative splicing, SR proteins have been reported to have many other activities. Studying the versatility of SR proteins poses challenges, but specific approaches can be used to unravel their activities, which can be applied to other multifunctional RBPs as well.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Gastroenterology & Hepatology
Emma Wischlen, Noemie Laverdure, Domitille Erard, Barbara Rohmer, Olivier Boillot, Remi Dubois, Alain Lachaux, Sophie Collardeau-Frachon, Valerie Hervieu, Jerome Dumortier
Summary: Post-transplantation evolution of progressive familial intrahepatic cholestasis type 2 patients can be complicated by antibody-induced bile salt export pump deficiency (AIBD). There is no consensus on its management. We describe a patient who presented two episodes, 9 years apart. The first episode was refractory to plasmapheresis and intravenous immunoglobulin (IVIG) started 2 months after AIBD onset, leading to graft loss. The second episode responded to plasmapheresis, IVIG and rituximab initiated less than 2 weeks after the beginning of symptoms, allowing for long-term recovery. This case suggests that intensive treatment with minimum delay after symptoms onset could sponsor a better evolution.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2023)
Article
Toxicology
L. Liu, Y. Yang, W. Li, Y. Li, X. Jiang, L. Wang
Summary: This study aimed to investigate the effects of Rifampicin (RFP) and Tanshinone IIA (TAN IIA) on bile salt export pump (BSEP) and explore the potential role of TAN IIA in treating RFP-induced cholestasis. The results showed that RFP inhibited the expression and function of BSEP, while TAN IIA reversed this inhibition.
HUMAN & EXPERIMENTAL TOXICOLOGY
(2022)
Article
Toxicology
Jing Zhao, Guochao Song, Fengyi Weng, Yue Li, Bin Zou, Jingyi Jin, Dongming Yan, Xin Sun, Chenghai Liu, Fu-rong Qiu
Summary: The aim of this study was to investigate the effect of TUDCA on ANIT-induced cholestasis in mice. TUDCA exacerbated cholestatic liver injury in wild-type mice by upregulating BSEP expression, increasing bile acid-dependent bile flow, and aggravating bile duct obstruction. However, TUDCA improved liver pathology and protected cholangiocytes against toxic bile acids in ANIT-induced Fxr(-/-) mice.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Nutrition & Dietetics
Greg Guthrie, Barbara Stoll, Shaji Chacko, Mahmoud Mohammad, Candace Style, Mariatu Verla, Oluyinka Olutoye, Deborah Schady, Charlotte Lauridsen, Nick Tataryn, Douglas Burrin
Summary: The study found that manipulating the phytosterol concentration in a soybean oil-based emulsion affected the onset and severity of cholestasis in preterm piglets. Higher phytosterol concentrations were associated with elevated serum markers of cholestasis, while the group with lower phytosterol concentration had lower levels of serum direct bilirubin.
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
(2022)
Article
Medicine, Research & Experimental
Guochao Song, Fengyi Weng, Bin Zou, Jing Zhao, Jingyi Jin, Dongming Yan, Kai Huang, Xin Sun, Chenghai Liu, Yiyang Hu, Yue Li, Furong Qiu
Summary: In this study, it was found that TUDCA protected against cholestatic liver injury by activating Fxr and Nrf2, as well as by inhibiting the CHOP-DR5-caspase-8 pathway to reduce apoptosis.
Article
Allergy
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Summary: Circulating autoantibodies are crucial for the diagnosis and classification of autoimmune hepatitis (AIH). The reference method for autoantibody testing remains indirect immunofluorescence, despite limitations. Further studies are needed to validate automated assays as reliable alternatives.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Review
Gastroenterology & Hepatology
Angelo Di Giorgio, Diego Vergani, Giorgina Mieli-Vergani
Summary: Sclerosing cholangitis is a rare chronic disorder characterized by inflammation and progressive fibrosis of the bile ducts. The most common form in children is associated with autoimmune features and inflammatory bowel disease. The disease can progress to biliary cirrhosis and end-stage liver disease, potentially requiring liver transplantation.
DIGESTIVE AND LIVER DISEASE
(2022)
Letter
Pediatrics
Marianne Samyn, Kai Hensel, Nedim Hadzic, Giorgina Mieli-Vergani
JOURNAL OF PEDIATRICS
(2022)
Review
Immunology
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Summary: Autoimmune hepatitis is an inflammatory liver disease affecting all ages, with type 1 and type 2 having different autoantibodies and predisposing factors, typically responding well to treatment with steroids and azathioprine.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Jonathon J. Graham, Sujit Mukherjee, Muhammad Yuksel, Rebeca Sanabria Mateos, Tengfei Si, Zhenlin Huang, Xiahong Huang, Hadil Abu Arqoub, Vishal Patel, Mark McPhail, Yoh Zen, Nigel Heaton, Maria Serena Longhi, Michael A. Heneghan, Rodrigo Liberal, Diego Vergani, Giorgina Mieli-Vergani, Yun Ma, Bu'Hussain Hayee
Summary: The study found that the gut homing hypothesis is not the primary driver of PSC, and aberrant recruitment of gut-derived T cells to the liver is also seen in other chronic liver diseases. This finding provides a new understanding of the pathogenesis of PSC and CLD.
Review
Gastroenterology & Hepatology
Simon Pape, Romee J. A. L. M. Snijders, Tom J. G. Gevers, Oliver Chazouilleres, George N. Dalekos, Gideon M. Hirschfield, Marco Lenzi, Michael Trauner, Michael R. Manns, John M. Vierling, Aldo J. Montano-Loza, Ansgar W. Lohse, Christoph Schramm, Joost P. H. Drenth, Michael A. Heneghan
Summary: The International Autoimmune Hepatitis Group proposed a consensus on response criteria and endpoints in autoimmune hepatitis, defining terms like complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment to guide future reporting.
JOURNAL OF HEPATOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Giorgina Mieli-Vergani, Yoh Zen, Diego Vergani
LIVER INTERNATIONAL
(2022)
Article
Genetics & Heredity
Giulia Romano, Federico Riccardi, Erica Bussani, Simone Vodret, Danilo Licastro, Isabella Ragone, Giuseppe Ronzitti, Elisabetta Morini, Susan A. Slaugenhaupt, Franco Pagani
Summary: This study successfully delivered ExSpeU1 small nuclear RNA using AAV9-U1-FD vector in a mouse model of FD, which increased the inclusion of ELP1 exon 20 and production of functional protein. The treatment rescued the majority of FD mouse mortality and improved motor function, renal function, and cardiac function. RNA-seq analysis showed minimal global changes in gene expression and splicing. This therapeutic strategy shows high specificity and potential for treating FD.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
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)