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REVIEW
Rolf Teschke
Drug induced liver injury (DILI) occurs in patients exposed to drugs at recommended doses that leads to idiosyncratic DILI and provides an excellent human model with well described clinical features, liver injury pattern, and diagnostic criteria, based on patients assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) as original method of 1993 or its update of 2016. Overall, 81,856 RUCAM based DILI cases have been published until mid of 2020, allowing now for an analysis of mechanistic issues of the disease...
April 3, 2023: International Journal of Molecular Sciences
#22
Marlone Cunha-Silva, Eloy Vianey Carvalho de França, Raquel Dias Greca, Daniel Ferraz de Campos Mazo, Larissa Bastos Eloy da Costa, Priscilla Brito Sena de Moraes, Clauber Teles Veiga, Guilherme Rossi Assis-Mendonça, Ilka de Fátima Santana Ferreira Boin, Raquel Silveira Bello Stucchi, Tiago Sevá-Pereira
COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive...
2023: Autopsy & Case Reports
#23
JOURNAL ARTICLE
Maho Yamashita, Akira Honda, Shin Shimoyama, Masahiro Umemura, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Nobuhito Kurono, Mayuko Ichimura-Shimizu, Koichi Tsuneyama, Teruo Miyazaki, Atsushi Tanaka, Patrick S C Leung, M Eric Gershwin, Takafumi Suda, Kazuhito Kawata
Primary biliary cholangitis (PBC) is a classic autoimmune disease due to the loss of tolerance to self-antigens. Bile acids (BA) reportedly play a major role in biliary inflammation and/or in the modulation of dysregulated immune responses in PBC. Several murine models have indicated that molecular mimicry plays a role in autoimmune cholangitis; however, they have all been limited by the relative failure to develop hepatic fibrosis. We hypothesized that species-specific differences in the BA composition between mice and humans were the primary reason for this limited pathology...
March 28, 2023: Journal of Autoimmunity
#24
JOURNAL ARTICLE
Sunil Taneja, Rohit Mehtani, Arka De, Suvradeep Mitra, Sahaj Rathi, Nipun Verma, Madhumita Premkumar, Ranjana Minz, Ajay Duseja, Ashim Das, Virendra Singh, Radha K Dhiman, Yogesh K Chawla
BACKGROUND AND AIMS: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. METHODS: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics...
2023: Journal of Clinical and Experimental Hepatology
#25
JOURNAL ARTICLE
Wojciech Jańczyk, Joanna B Bierła, Ilona Trojanowska, Aldona Wierzbicka-Rucińska, Bożena Cukrowska, Piotr Socha
Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig)...
February 17, 2023: Diagnostics
#26
JOURNAL ARTICLE
Charles Drummer, Fatma Saaoud, Nirag C Jhala, Ramon Cueto, Yu Sun, Keman Xu, Ying Shao, Yifan Lu, Huimin Shen, Ling Yang, Yan Zhou, Jun Yu, Sheng Wu, Nathaniel W Snyder, Wenhui Hu, Jia 'Joe' Zhuo, Yinghui Zhong, Xiaohua Jiang, Hong Wang, Xiaofeng Yang
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% of the population and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD ranges from simple steatosis (non-alcoholic fatty liver) to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs) and monocyte-derived macrophages, act as key players in the progression of NAFLD. Caspases are a family of endoproteases that provide critical connections to cell regulatory networks that sense disease risk factors, control inflammation, and mediate inflammatory cell death (pyroptosis)...
2023: Frontiers in Immunology
#27
Venkata Vinod Kumar Matli, David F Dies, Sudha Pandit, Gregory Wellman, James D Morris
Antimitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes in the mitochondrial membranes of biliary epithelial cells, resulting in progressive nonsuppurative biliary cholangitis. Up to 5% of patients lack these autoantibodies, termed antimitochondrial antibody-negative (AMA-neg) PBC. Although a somewhat new variant of AMA-pos PBC, it is not an overlapping syndrome. Few studies to date have described this phenomenon...
2023: Case Reports in Gastroenterology
#28
JOURNAL ARTICLE
Mirjam Kolev, Adela-Cristina Sarbu, Burkhard Möller, Britta Maurer, Florian Kollert, Nasser Semmo
BACKGROUND: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti -B cell activating factor, belimumab...
2023: Journal of translational autoimmunity
#29
JOURNAL ARTICLE
Mengyi Shen, Xiaoli Fan, Yi Shen, Xiaoze Wang, Ruiqi Wu, Yi Wang, Chen Huang, Shenglan Zhao, Yanyi Zheng, Ruoting Men, Xuefeng Luo, Li Yang
BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory liver disease that is associated with impaired self-tolerance. Myeloid-derived supprfessor cells (MDSCs) have been considered to exert counterregulatory effects on AIH. However, the specific mechanism underlying these effects is unclear. Herein, we investigated the efficacy and safety of MDSCs in protecting against AIH and explored the underlying mechanism. METHODS: Circulating and liver MDSC expression levels in 71 AIH patients and 47 healthy control (HC) individuals were detected by flow cytometry and immunohistochemistry...
December 12, 2022: International Immunopharmacology
#30
JOURNAL ARTICLE
Greta Codoni, Theresa Kirchner, Bastian Engel, Alejandra Maria Villamil, Cumali Efe, Albert Friedrich Stättermayer, Jan Philipp Weltzsch, Marcial Sebode, Christine Bernsmeier, Ana Lleo, Tom Jg Gevers, Limas Kupčinskas, Agustin Castiella, Jose Pinazo, Eleonora De Martin, Ingrid Bobis, Thomas Damgaard Sandahl, Federica Pedica, Federica Invernizzi, Paolo Del Poggio, Tony Bruns, Mirjam Kolev, Nasser Semmo, Fernando Bessone, Baptiste Giguet, Guido Poggi, Masayuki Ueno, Helena Jang, Gülsüm Özlem Elpek, Neşe Karadağ Soylu, Andreas Cerny, Heiner Wedemeyer, Diego Vergani, Giorgina Mieli-Vergani, M Isabel Lucena, Raul J Andrade, Yoh Zen, Richard Taubert, Benedetta Terziroli Beretta-Piccoli
BACKGROUND & AIMS: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. METHODS: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included...
January 2023: JHEP reports: innovation in hepatology
#31
JOURNAL ARTICLE
Rachel Wolfe, Paige Heiman, Olivia D'Annibale, Anuradha Karunanidhi, Alyssa Powers, Marianne Mcguire, Bianca Seminotti, Steven F Dobrowolski, Miguel Reyes-Múgica, Kathryn S Torok, Al-Walid Mohsen, Jerry Vockley, Lina Ghaloul-Gonzalez
Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities...
December 2022: Molecular Genetics and Metabolism Reports
#32
REVIEW
Boris D Hristov
Glutathione (GSH) is the most abundant thiol antioxidant in the human body and serves many important biochemical functions, including the regulation of vitamins, such as vitamins D, E, and C, and detoxification of drugs and toxins. As a powerful antioxidant, GSH is particularly important as a regulator of mitochondrial metabolism and a free radical scavenger that limits oxidative damage to cellular components. Low GSH levels have been associated with many chronic pro-inflammatory conditions, such as metabolic syndrome, cardiovascular, renal, and hepatic disease, as well as neurodegenerative conditions and autoimmune diseases...
September 2022: Curēus
#33
JOURNAL ARTICLE
Ariane Soldatos, Thomas B Nutman, Tory Johnson, Scott F Dowell, James J Sejvar, Michael R Wilson, Joseph L DeRisi, Sara K Inati, Catherine Groden, Colleen Evans, Elise M O'Connell, Bernard Opar Toliva, Jane R Aceng, Josephine Aryek-Kwe, Camilo Toro, Constantine A Stratakis, A Gretchen Buckler, Cathy Cantilena, Tara N Palmore, Audrey Thurm, Eva H Baker, Richard Chang, Harper Fauni, David Adams, Ellen F Macnamara, C Christopher Lau, May Christine V Malicdan, Barbara Pusey-Swerdzewski, Robert Downing, Sudhir Bunga, Jerry D Thomas, William A Gahl, Avindra Nath
The etiology of Nodding Syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with Nodding Syndrome, investigate potential contributors to disease etiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for Nodding Syndrome and with a conducive family structure for genomic analyses...
October 1, 2022: Brain
#34
JOURNAL ARTICLE
Liqing Cheng, Zhanqi Wei, Zaopeng Yang, Renlin Lu, Ming Yang, Muchun Yu, Naixue Yang, Shulin Li, Mingyi Gao, Xueqiang Zhao, Xin Lin
Carma3 is an intracellular scaffolding protein that can form complex with Bcl10 and Malt1 to mediate G protein-coupled receptor- or growth factor receptor-induced NF-κB activation. However, the in vivo function of Carma3 has remained elusive. Here, by establishing a Con A-induced autoimmune hepatitis model, we show that liver injury is exacerbated in Carma3 -/- mice. Surprisingly, we find that the Carma3 expression level is higher in liver sinusoidal endothelial cells (LSECs) than in hepatocytes in the liver...
August 1, 2022: Journal of Immunology
#35
JOURNAL ARTICLE
Fu-Li Shi, Si-Tao Ni, Shi-Qi Luo, Bo Hu, Rong Xu, Si-Ying Liu, Xiao-di Huang, Bo Zeng, Qi-Qi Liang, Si-Yuan Chen, Jia-Hao Qiu, Xian-Hui He, Qing-Bing Zha, Dong-Yun Ouyang
Dimethyl fumarate (DMF) is a fumaric acid derivative clinically approved for the treatment of some inflammatory diseases, but the underlying mechanism for its therapeutic effects remains incompletely understood. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation has critical roles in innate immune responses to various infections and sterile inflammations. In this study, we aimed to explore whether DMF affects auto-immune hepatitis (AIH) in mice induced by concanavalin A (Con A) by modulating NLRP3 inflammasome activation...
July 2022: International Immunopharmacology
#36
JOURNAL ARTICLE
Saleh A Alqahtani, Rose Chami, Dua Abuquteish, Shannon M Vandriel, Charesse Yap, Liyana Kukkadi, Aishwarya Parmar, Amrita Mundh, Eve A Roberts, Binita M Kamath, Iram Siddiqui
BACKGROUND AND AIMS: Wilson disease (WD) has diverse presentations that frequently mimic other liver diseases. Distinguishing WD from non-alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH), can be difficult and has critical implications for medical management. This study aimed to examine the utility of histological features of WD in children compared to those with NAFLD and AIH. METHODS: A review of liver biopsy slides was performed in children with a clinical and/or genetic diagnosis of WD, seen at the Hospital for Sick Children between 1981 and 2019 and compared to controls with NAFLD and AIH...
November 2022: Liver International: Official Journal of the International Association for the Study of the Liver
#37
JOURNAL ARTICLE
Ciro Romano, Olga Tortorella, Liliana Dalla Mora, Dario Di Stasio, Ausilia Sellitto, Luigi Elio Adinolfi, Aldo Marrone
Background: Chronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients. Methods: The medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication...
2022: Frontiers in Immunology
#38
JOURNAL ARTICLE
Yanli Hou, Wenyu Ding, Peishan Wu, Changqing Liu, Lina Ding, Junjun Liu, Xiaolei Wang
BACKGROUND: Type 1 diabetes mellitus (T1D) is a worldwide health priority due to autoimmune destruction and is associated with an increased risk of multiorgan complications. Among these complications, effective interventions for liver injury, which can progress to liver fibrosis and hepatocellular carcinoma, are lacking. Although stem cell injection has a therapeutic effect on T1D, whether it can cure liver injury and the underlying mechanisms need further investigation. METHODS: Sprague-Dawley rats with streptozotocin (STZ)-induced T1D were treated with adipose-derived stem cell (ADSC) or PBS via the tail vein formed the ADSC group or STZ group...
April 1, 2022: Stem Cell Research & Therapy
#39
JOURNAL ARTICLE
Guillermo Muñoz-Sánchez, Albert Pérez-Isidro, Iñaki Ortiz de Landazuri, Antonio López-Gómez, Luz Yadira Bravo-Gallego, Milagros Garcia-Ormaechea, Maria Rosa Julià, Odette Viñas, Estíbaliz Ruiz-Ortiz, On Behalf Of The Geai-Sei Workshop Participants
Autoantibody detection is the cornerstone of autoimmune liver diseases (AILD) diagnosis. Standardisation of working algorithms among autoimmunity laboratories, as well as being aware of the sensitivity and specificity of various commercial techniques in daily practice, are still necessary. The aim of this nationwide study is to report the results of the 2020 Autoimmunity Workshop organised by the Autoimmunity Group of the Spanish Society of Immunology and to provide useful information to clinicians and laboratory specialists to improve the management of autoantibody detection in AILD diagnoses...
March 12, 2022: Diagnostics
#40
JOURNAL ARTICLE
Ali Duran, Alev Çetin Duran, İsmail Taşkıran
Autoantibodies are frequently detected in the presence of autoimmune liver diseases (ALD) [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)] and are widely used to classify the disease clinically. The aim of this study was to investigate the contribution of autoantibodies for the diagnosis of ALD and the identification of other accompanying systemic autoimmune rheumatic diseases (SARD). In addition, it was aimed to compare the results of indirect immunofluorescence (IIF) antinuclear antibody (ANA) patterns and extractable nuclear antigen (ENA) antibodies...
January 2022: Mikrobiyoloji Bülteni
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