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https://www.readbyqxmd.com/read/29337684/hepatotoxicity-associated-with-statins
#1
Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk, Yağmur Özkan
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29335546/transcription-factors-orchestrate-dynamic-interplay-between-genome-topology-and-gene-regulation-during-cell-reprogramming
#2
Ralph Stadhouders, Enrique Vidal, François Serra, Bruno Di Stefano, François Le Dily, Javier Quilez, Antonio Gomez, Samuel Collombet, Clara Berenguer, Yasmina Cuartero, Jochen Hecht, Guillaume J Filion, Miguel Beato, Marc A Marti-Renom, Thomas Graf
Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and MYC offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We have recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we used this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin-state dynamics...
January 15, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29324638/molecular-research-on-drug-induced-liver-injury
#3
EDITORIAL
Rolf Teschke, Gaby Danan
Drugs may cause liver injury in a few susceptible individuals, but the molecular events that lead to this idiosyncratic, largely dose-independent and non-predictable drug-induced liver injury (DILI) are mostly unknown, since animal models to explore the pathogenetic mechanisms of human idiosyncratic DILI are not yet reliable.[...].
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29323538/clinical-characteristics-and-outcomes-of-traditional-chinese-medicine-induced-liver-injury-a-systematic-review
#4
Ran Wang, Xingshun Qi, Eric Yoshida, Nahum Mendez-Sanchez, Rolf Teschke, Mingyu Sun, Xu Liu, Chunping Su, Jiao Deng, Han Deng, Feifei Hou, Xiaozhong Guo
BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. AIMS: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). METHODS: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched...
January 11, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29310474/low-prevalence-of-hepatitis-e-in-iceland-a-seroepidemiological-study
#5
Arthur Löve, Thora B Björnsdottir, Sigurdur Olafsson, Einar S Björnsson
OBJECTIVE: Hepatitis E virus (HEV) infection has been reported to be more prevalent in the developed countries than previously thought. HEV infection is an important differential diagnosis in patients with drug-induced liver injury (DILI). The prevalence of hepatitis E was investigated in the general population of Iceland, among pig farmers and patients with DILI. MATERIALS AND METHODS: Serum samples were tested for hepatitis E IgG, with two commercial ELISA tests: Diagnostic Bioprobes Srl...
January 8, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29309877/development-of-a-mechanistic-biokinetic-model-for-hepatic-bile-acid-handling-to-predict-possible-cholestatic-effects-of-drugs
#6
Sylvia Notenboom, Karl M Weigand, Johannes H Proost, Marola M van Lipzig, Evita van de Steeg, Petra H H van den Broek, Rick Greupink, Frans G M Russel, Geny M M Groothuis
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic) intrahepatic concentrations of bile acids with subsequent cell injury. In order to investigate the possibilities for in silico prediction of cholestatic effects of drugs, we developed a mechanistic biokinetic model for human liver bile acid handling populated with human in vitro data...
January 5, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29308212/-the-efficacy-of-extracorporeal-liver-support-with-molecular-adsorbent-recirculating-system-in-severe-drug-induced-liver-injury
#7
Jaishvi Eapen, Rotimi Ayoola, Ram M Subramanian
We report a case of a 26-year-old man with no significant medical history, who presented with fatigue, pruritus, jaundice, dark urine and clay colored stool for one month. He had been taking methyl-1-etiochoenolol-epietiocholanolone, an androgenic anabolic steroid (AAS). He was initially found to have a total bilirubin (Tbili) of 6 mg/dL. He discontinued the AAS but the patients' symptoms worsened and Tbili increased to 36 mg/d. This prompted inpatient management of his drug-induced liver injury (DILI). Molecular adsorbent recirculating system (MARS) is an extracorporeal liver support system that replaces the detoxification function of the liver...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29307848/herbal-and-dietary-supplement-induced-liver-injuries-in-the-spanish-dili-registry
#8
Inmaculada Medina-Caliz, Miren Garcia-Cortes, Andres Gonzalez-Jimenez, Maria R Cabello, Mercedes Robles-Diaz, Judith Sanabria-Cabrera, Rocio Sanjuan-Jimenez, Aida Ortega-Alonso, Beatriz García-Muñoz, Inmaculada Moreno, Miguel Jimenez-Perez, M Carmen Fernandez, Pere Ginés, Martin Prieto, Isabel Conde, Hacibe Hallal, German Soriano, Eva Roman, Agustin Castiella, Encarnacion Blanco-Reina, Maria R Montes, Marta Quiros-Cano, Flores Martin-Reyes, M Isabel Lucena, Raul J Andrade
BACKGROUND & AIMS: There have been increasing reports of liver injury associated with use of herbal and dietary supplements, likely due to easy access to these products and beliefs among consumers that they are safer or more effective than conventional medications. We aimed to evaluate clinical features and outcomes of patients with herbal and dietary supplement-induced liver injuries included in the Spanish DILI Registry. METHODS: We collected and analyzed data on demographic and clinical features, along with biochemical parameters, of 32 patients with herbal and dietary supplement-associated liver injury reported to the Spanish DILI registry from 1994 through 2016...
January 4, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29306044/heavy-consumption-of-alcohol-is-not-associated-with-worse-outcomes-in-patients-with-idiosyncratic-drug-induced-liver-injury-compared-to-non-drinkers
#9
Lara Dakhoul, Marwan Ghabril, Jiezhun Gu, Victor Navarro, Naga Chalasani, Jose Serrano
BACKGROUND & AIMS: The relationship between alcohol consumption and idiosyncratic drug induced liver injury (DILI) is not well understood. We investigated the relationship between heavy consumption of alcohol and characteristics and outcomes of patients with DILI enrolled in the Drug-induced Liver Injury Network (DILIN) prospective study. METHODS: We collected data from 1198 individuals with definite, highly likely, or probable DILI enrolled in the DILIN study from September 2004 through April 2016...
January 3, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29287080/serum-apolipoprotein-a1-and-haptoglobin-in-patients-with-suspected-drug-induced-liver-injury-dili-as-biomarkers-of-recovery
#10
Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Yen Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu, Dominique Thabut, Marika Rudler, Vincent Thibault, Ina Schuppe-Koistinen, Dominique Bonnefont-Rousselot, Bernard Hainque, Françoise Imbert-Bismut, Michael Merz, Gerd Kullak-Ublick, Raul Andrade, Florian van Boemmel, Eckart Schott, Thierry Poynard
BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled...
2017: PloS One
https://www.readbyqxmd.com/read/29277727/antimicrobial-resistance-in-urine-and-skin-isolates-in-timor-leste
#11
Ian Marr, Nevio Sarmento, Matt O'Brien, Karl Lee, Celia Gusmao, Gloria de Castro, Sonja Janson, Steven Y C Tong, Rob W Baird, Joshua R Francis
OBJECTIVES: High rates of antimicrobial resistance are seen throughout Southeast Asia. Limited antimicrobial resistance data exists for Timor-Leste, which is situated on the south-eastern portion of the Malay Archipelago. The purpose of this study was to identify antimicrobial resistance in bacteria isolated from urine and skin swabs from patients in Dili, Timor-Leste. METHODS: Urine and skin swabs were collected from symptomatic patients and processed for bacterial culture in Timor-Leste...
December 22, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29274889/new-onset-autoimmune-hepatitis-during-anti-tumor-necrosis-factor-alpha-treatment-in-children
#12
Amanda Ricciuto, Binita M Kamath, Thomas D Walters, Karen Frost, Nicholas Carman, Peter C Church, Simon C Ling, Anne M Griffiths
OBJECTIVES: To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. STUDY DESIGN: We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center...
December 21, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29247427/clinical-spectrum-and-outcome-of-pediatric-drug-induced-liver-injury
#13
Aditi Kumar, Vikrant Sood, Rajeev Khanna, Sanjeev Kumar Verma, Nikhil Mehra, Dinesh Rawat, Seema Alam
Limited literature is available in pediatric population regarding drug-induced liver injury (DILI) making it a diagnostic challenge. This study was thus planned to determine the clinical spectrum and the outcome of DILI in children. All patients with DILI under 18 y of age were retrospectively reviewed and details regarding clinical presentation, Roussel Uclaf Causality Assessment Method (RUCAM) scale, drugs implicated, biochemical abnormalities and outcome were noted. DILI constituted 3.7% of all children with liver disease...
December 16, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29235390/mir-122-and-other-micrornas-as-potential-circulating-biomarkers-of-drug-induced-liver-injury
#14
Lawrence S Howell, Lucy Ireland, B Kevin Park, Christopher E Goldring
Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers. Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI...
December 15, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29229971/development-of-decision-forest-models-for-prediction-of-drug-induced-liver-injury-in-humans-using-a-large-set-of-fda-approved-drugs
#15
Huixiao Hong, Shraddha Thakkar, Minjun Chen, Weida Tong
Drug-induced liver injury (DILI) presents a significant challenge to drug development and regulatory science. The FDA's Liver Toxicity Knowledge Base (LTKB) evaluated >1000 drugs for their likelihood of causing DILI in humans, of which >700 drugs were classified into three categories (most-DILI, less-DILI, and no-DILI). Based on this dataset, we developed and compared 2-class and 3-class DILI prediction models using the machine learning algorithm of Decision Forest (DF) with Mold2 structural descriptors...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229868/sex-dependent-differences-in-inflammatory-responses-during-liver-regeneration-in-a-murine-model-of-acute-liver-injury
#16
Debora Bizzaro, Marika Crescenzi, Rosa Di Liddo, Diletta Arcidiacono, Andrea Cappon, Thomas Bertalot, Vincenzo Amodio, Alessia Tasso, Annalisa Stefani, Valentina Bertazzo, Giacomo Germani, Chiara Frasson, Giuseppe Basso, Pierpaolo Parnigotto, Malcolm Ronald Alison, Patrizia Burra, Maria Teresa Conconi, Francesco Paolo Russo
A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and sacrificed after 3, 5 and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide...
December 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29222960/drug-induced-acute-liver-failure-in-children-and-adults-results-of-a-single-center-study-of-128-patients
#17
Harshad Devarbhavi, Mallikarjun Patil, Vishnu Vardhan Reddy, Rajvir Singh, Tarun Joseph, Deepak Ganga
BACKGROUND AND AIMS: Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analyzed the predictors of mortality and their relationship with MELD, Kings College criteria (KCC) and ALFSG prognostic index. METHODS: We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017)...
December 9, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29221514/yield-of-brain-mri-in-clinically-diagnosed-epilepsy-in-the-kingdom-of-bhutan-a-prospective-study
#18
Veronica Bruno, Joshua P Klein, Dechen Nidup, Damber K Nirola, Lhab Tshering, Sonam Deki, Sarah J Clark, Kristin A Linn, Russell T Shinohara, Chencho Dorji, Dili Ram Pokhrel, Ugyen Dema, Farrah J Mateen
BACKGROUND: People with epilepsy (PWE) in low- and middle-income countries may not access the health resources that are considered optimal for epilepsy diagnosis. The diagnostic yield of magnetic resonance imaging (MRI) has not been well studied in these settings. OBJECTIVES: To report the diagnostic yield of brain MRI and identify clinical associations of abnormal MRI findings among PWE in a neurocysticercosis-endemic, resource-limited setting and to identify the proportion and putative structural brain causes of drug-resistant epilepsy...
May 2017: Annals of Global Health
https://www.readbyqxmd.com/read/29217891/trimethoprim-sulfamethoxazole-induced-hepatotoxicity-in-a-renal-transplant-patient
#19
R Slim, N Asmar, C Yaghi, K Honein, R Sayegh, D Chelala
Drug-induced liver injury (DILI) represents liver damage from various therapeutic drugs. Antimicrobials are among the most common causes of DILI. We report a case of hepatic toxicity due to Trimethoprim-sulfamethoxazole (TMP-SMX) in a patient who underwent renal transplantation. Diagnosis has been made after a careful history taking, exclusion of competing etiologies and reversal of biochemical abnormalities after withdrawal of the antibiotic. TMP-SMX liver toxicity is well known but remains unpredictable and is rarely reported...
November 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/29203276/effect-of-ugt2b7-2-and-cyp2c8-4-polymorphisms-on-diclofenac-metabolism
#20
Katarzyna E Lazarska, Stefan J Dekker, Nico P E Vermeulen, Jan N M Commandeur
The use of diclofenac is associated with rare but severe drug-induced liver injury (DILI) in a very small number of patients. The factors which predispose susceptible patients to hepatotoxicity of diclofenac are still incompletely understood. Formation of protein-reactive metabolites by UDP-glucuronosyl transferases and cytochromes P450 is commonly considered to play an important role, as indicated by the detection of covalent protein adducts and antibodies in the serum of patients suffering from diclofenac-induced liver injury...
December 1, 2017: Toxicology Letters
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