261 results on '"Stephens, Camilla"'
Search Results
52. Mitochondrial Superoxide Dismutase and Glutathione Peroxidase in Idiosyncratic Drug-Induced Liver Injury
- Author
-
Lucena, Isabel M., García-Martín, Elena, Andrade, Raúl J., Martínez, Carmen, Stephens, Camilla, Ruiz, Jhon D., Ulzurrun, Eugenia, Fernandez, Carmen M., Romero-Gomez, Manuel, Castiella, Augustin, Planas, Ramon, Durán, José Antonio, De Dios, Ana Melcón, Guarner, Carlos, Soriano, German, Borraz, Yolanda, and Agundez, José A. G.
- Published
- 2010
- Full Text
- View/download PDF
53. TEATIME TREATS.
- Author
-
Mamam, Bonne, Burton, Lucy, Lama, Holy, Stanton, Florence, Thomas, Sarah J., Hope, Jenna, and Stephens, Camilla
- Published
- 2022
54. BISCUIT HEAVEN.
- Author
-
Stephens, Camilla, Burton, Lucy, and Thomas, Sarah J.
- Published
- 2022
55. Quick & easy.
- Author
-
Payne, Cassidy, Beetroot, Love, Radley, Day, Auzbikaviciute, Aiste, Erickson, Freya, and Stephens, Camilla
- Published
- 2022
56. Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions
- Author
-
Nicoletti, Paola, Barrett, Sarah, McEvoy, Laurence, Daly, Ann K., Aithal, Guruprasad, Isabel Lucena, M., Andrade, Raul J., Wadelius, Mia, Hallberg, Pär, Stephens, Camilla, Bjornsson, Einar S., Friedmann, Peter, Kainu, Kati, Laitinen, Tarja, Marson, Anthony, Molokhia, Mariam, Phillips, Elizabeth, Pichler, Werner, Romano, Antonino, Shear, Neil, Sills, Graeme, Tanno, Luciana K., Swale, Ashley, Floratos, Aris, Shen, Yufeng, Nelson, Matthew R., Watkins, Paul B., Daly, Mark J., Morris, Andrew P., Alfirevic, Ana, Pirmohamed, Munir, Nicoletti, Paola, Barrett, Sarah, McEvoy, Laurence, Daly, Ann K., Aithal, Guruprasad, Isabel Lucena, M., Andrade, Raul J., Wadelius, Mia, Hallberg, Pär, Stephens, Camilla, Bjornsson, Einar S., Friedmann, Peter, Kainu, Kati, Laitinen, Tarja, Marson, Anthony, Molokhia, Mariam, Phillips, Elizabeth, Pichler, Werner, Romano, Antonino, Shear, Neil, Sills, Graeme, Tanno, Luciana K., Swale, Ashley, Floratos, Aris, Shen, Yufeng, Nelson, Matthew R., Watkins, Paul B., Daly, Mark J., Morris, Andrew P., Alfirevic, Ana, and Pirmohamed, Munir
- Abstract
Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 x 10(-9)) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 x 10(-9)) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.
- Published
- 2019
- Full Text
- View/download PDF
57. Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug‐Induced Liver Injury in the Spanish DILI Registry.
- Author
-
Sanabria‐Cabrera, Judith, Sanjuán‐Jiménez, Rocío, Clavijo, Encarnación, Medina‐Cáliz, Inmaculada, González‐Jiménez, Andrés, García‐Cortés, Miren, Ortega‐Alonso, Aida, Jiménez‐Pérez, Miguel, González‐Grande, Rocío, Stephens, Camilla, Robles‐Díaz, Mercedes, Lucena, M Isabel, and Andrade, Raúl J.
- Subjects
HEPATITIS E virus ,VIRUS diseases ,LIVER injuries ,HEPATITIS E ,DIAGNOSIS ,HEPATITIS B - Abstract
Background and Aims: Drug‐induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti‐HEV seroprevalence rate. Methods: An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti‐HEV Immunoglobulin (Ig) G antibodies were analysed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n = 144), HEV antigen (Ag) and anti‐HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT‐PCR was performed externally in eight patients. Results: Out of 144 patients, 12 (8%) were positive for anti‐HEV IgM, mean age was 61 years. Underlying hepatic diseases (OR = 23.4, P <.001) and AST peak >20 fold upper limit of normal (OR = 10.9, P =.002) were associated with the diagnosis of acute hepatitis E. The overall anti‐HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). Conclusions: HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
58. Shared Genetic Risk Factors Across Carbamazepine‐Induced Hypersensitivity Reactions
- Author
-
Nicoletti, Paola, primary, Barrett, Sarah, additional, McEvoy, Laurence, additional, Daly, Ann K., additional, Aithal, Guruprasad, additional, Lucena, M. Isabel, additional, Andrade, Raul J., additional, Wadelius, Mia, additional, Hallberg, Pär, additional, Stephens, Camilla, additional, Bjornsson, Einar S., additional, Friedmann, Peter, additional, Kainu, Kati, additional, Laitinen, Tarja, additional, Marson, Anthony, additional, Molokhia, Mariam, additional, Phillips, Elizabeth, additional, Pichler, Werner, additional, Romano, Antonino, additional, Shear, Neil, additional, Sills, Graeme, additional, Tanno, Luciana K., additional, Swale, Ashley, additional, Floratos, Aris, additional, Shen, Yufeng, additional, Nelson, Matthew R., additional, Watkins, Paul B., additional, Daly, Mark J., additional, Morris, Andrew P., additional, Alfirevic, Ana, additional, and Pirmohamed, Munir, additional
- Published
- 2019
- Full Text
- View/download PDF
59. FRI-078-Serious liver injury induced by nimesulide: An international collaboration reporting 57 cases
- Author
-
Bessone, Fernando, primary, Hernandez, Nélia, additional, Mendizabal, Manuel, additional, Ridruejo, Ezequiel, additional, Gualano, Gisela Lorena, additional, Fassio, Eduardo, additional, Peralta, Mirta, additional, Fainboim, Hugo, additional, Anders, Maria Margarita, additional, Tanno, Federico, additional, Tano, Hugo Enrique, additional, Filho, Raymundo Parana, additional, Medina-Caliz, I, additional, Robles, Mercedes, additional, Stephens, Camilla, additional, Colombato, Luis Arturo, additional, Reggiardo, Maria Virginia, additional, Lucena, Maria Isabel, additional, and Andrade, Raul J., additional
- Published
- 2019
- Full Text
- View/download PDF
60. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury
- Author
-
Ortega-Alonso, Aida, Stephens, Camilla, Isabel Lucena, M., Andrade, Raul J., [Ortega-Alonso, Aida] Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Enfermedades Digest & Farmacol C, E-29071 Malaga, Spain, [Stephens, Camilla] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain, [Isabel Lucena, M.] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain, [Andrade, Raul J.] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain, Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional-FEDER, Agencia Espanola del Medicamento, and Instituto de Salud Carlos III
- Subjects
Salt export pump ,Rheumatoid-arthritis ,Nonhepatotoxic drugs ,Failure ,risk factors ,Covalent binding data ,Hepatitis-c virus ,Induced hepatotoxicity ,DILI ,Oral medications ,Autoimmune hepatitis ,drug-induced liver injury ,Antiretroviral therapy - Abstract
Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies.
- Published
- 2016
61. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study
- Author
-
Nicoletti, Paola, Aithal, Guruprasad P., Bjornsson, Einar S., Andrade, Raul J., Sawle, Ashley, Arrese, Marco, Barnhart, Huiman X., Bondon-Guitton, Emmanuelle, Hayashi, Paul H., Bessone, Fernando, Carvajal, Alfonso, Cascorbi, Ingolf, Cirulli, Elizabeth T., Chalasani, Naga, Conforti, Anita, Coulthard, Sally A., Daly, Mark J., Day, Christopher P., Dillon, John F., Fontana, Robert J., Grove, Jane I., Kullak-Ublick, Gerd A., Laitinen, Tarja, Larrey, Dominique, Lucena, M. Isabel, Maitland-van der Zee, Anke H., Martin, Jennifer H., Molokhia, Mariam, Pirmohamed, Munir, Powell, Elizabeth E., Qin, Shengying, Serrano, Jose, Stephens, Camilla, Stolz, Andrew, Wadelius, Mia, Watkins, Paul B., Floratos, Aris, Shen, Yufeng, Nelson, Matthew R., Urban, Thomas J., and Daly, Ann K.
- Subjects
side effect ,liver damage ,anti-fungal agent ,medication - Abstract
Background & aims: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors.Methods: We performed a GWAS of 862 persons with DILI and 10588 population-matched controls. The first set of cases was recruited prior to May 2009 in Europe (n=137) or the USA (n=274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the USA and South America. For the GWAS, we included only cases of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze human leukocyte antigen (HLA) genes and single nucleotide polymorphisms (SNPs). After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs.Results: We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% CI, 1.9–3.8; P=2.4x10–8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6–2.5; P=9.7x10–9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidinerelated DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant, genome wide, for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the LRBA gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6–2.7; P=4.8x10–9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR=5.4; 95% CI, 3.0–9.5; P=7.1x10–9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224Conclusions: In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non–drug-specific risk factors.
- Published
- 2017
62. Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study
- Author
-
Nicoletti, Paola, Aithal, Guruprasad P., Bjornsson, Einar S., Andrade, Raul J., Sawle, Ashley, Arrese, Marco, Barnhart, Huiman X., Bondon-Guitton, Emmanuelle, Hayashi, Paul H., Bessone, Fernando, Carvajal, Alfonso, Cascorbi, Ingolf, Cirulli, Elizabeth T., Chalasani, Naga, Conforti, Anita, Coulthard, Sally A., Daly, Mark J., Day, Christopher P., Dillon, John F., Fontana, Robert J., Grove, Jane I., Hallberg, Par, Hernandez, Nelia, Ibanez, Luisa, Kullak-Ublick, Gerd A., Laitinen, Tarja, Larrey, Dominique, Lucena, M. Isabel, Maitland-van der Zee, Anke H., Martin, Jennifer H., Molokhia, Mariam, Pirmohamed, Munir, Powell, Elizabeth E., Qin, Shengying, Serrano, Jose, Stephens, Camilla, Stolz, Andrew, Wadelius, Mia, Watkins, Paul B., Floratos, Aris, Shen, Yufeng, Nelson, Matthew R., Urban, Thomas J., Daly, Ann K., Int Drug-Induced Liver Injury Cons, Drug-Induced Liver Injury Network, Int Serious Adverse Events Consort, APH - Personalized Medicine, Pulmonology, Clinicum, Department of Medicine, and Keuhkosairauksien yksikkö
- Subjects
0301 basic medicine ,Oncology ,Male ,Antifungal Agents ,Liver Damage ,Genes, MHC Class I ,Genome-wide association study ,SUSCEPTIBILITY ,Medication ,Fenofibrate ,CHOLESTATIC HEPATITIS ,CLASS-I ,Sertraline ,Odds Ratio ,Medicine ,POPULATION ,Hypolipidemic Agents ,education.field_of_study ,anti-fungal agent ,Gastroenterology ,Middle Aged ,Antidepressive Agents ,3. Good health ,Phenotype ,Chromosomes, Human, Pair 2 ,Platelet aggregation inhibitor ,medication ,Female ,Chemical and Drug Induced Liver Injury ,medicine.medical_specialty ,Ticlopidine ,side effect ,Population ,PEPTIDE REPERTOIRE ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Naphthalenes ,Polymorphism, Single Nucleotide ,Article ,White People ,03 medical and health sciences ,liver damage ,Internal medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,education ,Allele frequency ,Terbinafine ,Alleles ,Hepatology ,HLA-A Antigens ,business.industry ,LRBA DEFICIENCY ,Odds ratio ,Side Effect ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,Anti-Fungal Agent ,T-CELLS ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,INDUCED HEPATOTOXICITY ,Platelet Aggregation Inhibitors ,Genome-Wide Association Study - Abstract
Background & Aims We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. Methods We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. Results We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9−3.8; P = 2.4 × 10−8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6−2.5; P = 9.7 × 10−9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6−2.7; P = 4.8 × 10−9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0−9.5; P = 7.1 × 10−9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. Conclusions In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non−drug-specific risk factors.
- Published
- 2016
63. The influence of drug properties and host factors on delayed onset of symptoms in drug‐induced liver injury
- Author
-
Gonzalez‐Jimenez, Andres, primary, McEuen, Kristin, additional, Chen, Minjun, additional, Suzuki, Ayako, additional, Robles‐Diaz, Mercedes, additional, Medina‐Caliz, Inmaculada, additional, Bessone, Fernando, additional, Hernandez, Nelia, additional, Arrese, Marco, additional, Parana, Raymundo, additional, Lucena, M. Isabel, additional, Stephens, Camilla, additional, and Andrade, Raúl J., additional
- Published
- 2018
- Full Text
- View/download PDF
64. Genetic risk factors in the development of idiosyncratic drug-induced liver injury
- Author
-
Stephens, Camilla, Lucena, M Isabel, and Andrade, Raúl J
- Abstract
ABSTRACTIntroduction: Idiosyncratic drug-induced liver injury (DILI) is a challenging condition with widespread implications. The underlying mechanism of DILI is not yet fully elucidated, but genetic predispositions are believed to contribute to DILI susceptibility. The identification of genetic risk factors has been a goal in DILI research for more than two decades.Areas covered: Here we provide an overview of genetic studies in DILI performed to date and outline polymorphisms identified to have a potential role in DILI development. This review covers both earlier candidate gene studies and more recent genome-wide association studies. The clinical applications of these findings are also discussed.Expert opinion: Various polymorphisms have been identified as associated with DILI susceptibility, but all of these have not been confirmed in independent studies or contradictive findings are available. Genome-wide significant associations between distinct HLA risk alleles and DILI due to specific causative agents strengthen the hypothesis that DILI is partially immune-mediated. These HLA alleles generally have low positive predictive value and are therefore not useful in preemptive tests to reduce DILI incidences, but can aid DILI diagnosis and clinical decision-making.
- Published
- 2021
- Full Text
- View/download PDF
65. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate–Induced Liver Injury in Spanish Patients
- Author
-
Stephens, Camilla, Moreno-Casares, Antonia, López-Nevot, Miguel-Ángel, García-Cortés, Miren, Medina-Cáliz, Inmaculada, Hallal, Hacibe, Soriano, German, Roman, Eva, Ruiz-Cabello, Francisco, Romero-Gómez, Manuel, Lucena, M. Isabel, Andrade, Raúl J., Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, European Commission, Agencia Española de Medicamentos y Productos Sanitarios, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), [Stephens,C, García-Cortés,M, Medina-Cáliz,I, Lucena,MI, Andrade,RJ] Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Málaga, Spain. [Moreno-Casares,A, López-Nevot,MA] Unidad de Gestión Clínica de Laboratorio, Departamento de Bioquímica y Biología Molecular III/Inmunología, Instituto de Investigación Biosanitario de Granada, Complejo Hospitalario de Granada, Universidad de Granada, Granada, Spain. [Hallal,H, Ruiz-Cabello,F] Servicio de Aparato Digestivo, Hospital Morales Meseguer, Murcia, Spain. [Soriano,G, Roman,E] Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain. [Roman,E] Escola Universitària d’Infermeria-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. [Romero-Gomez,M] Unidad de Gestión Clínica de Aparato Digestivo Intercentros, Hospitales Universitarios Virgen Macarena-Virgen del Rocio, CIBERehd, Seville, Spain., and The present study has been supported by grants of the Instituto de Salud Carlos III co-founded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI12/00378, SAS-PI-0239/2012, AC-0073-2013) and by the Agencia Española del Medicamento. CIBERehd is funded by Instituto de Salud Carlos III.
- Subjects
0301 basic medicine ,Drug-induced liver injury ,Lymphocyte ,Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands [Medical Subject Headings] ,Epitope ,immune response ,Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Genotype ,Pharmacology (medical) ,Receptor ,Amoxicilina ,Epítopos ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Pseudogenes [Medical Subject Headings] ,Original Research ,pharmacogenetics ,receptor/ligand ,education.field_of_study ,Diseases::Neoplasms [Medical Subject Headings] ,Células asesinas naturales ,Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings] ,Neoplasias ,Humanos ,HLA ,medicine.anatomical_structure ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings] ,Haplotipos ,Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings] ,Receptor/ligand ,drug-induced liver injury ,hepatotoxicity ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Clavulanic Acids::Clavulanic Acid [Medical Subject Headings] ,Population ,Human leukocyte antigen ,Biology ,Variación genética ,Subgrupos linfocitarios ,03 medical and health sciences ,Seudogenes ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin [Medical Subject Headings] ,Immune system ,Ácido clavulánico ,Enfermedades autoinmunes ,Diseases::Immune System Diseases::Autoimmune Diseases [Medical Subject Headings] ,medicine ,Immune response ,education ,Ligandos ,Pharmacology ,Receptores KIR ,Diseases::Substance-Related Disorders::Poisoning::Drug-Induced Liver Injury [Medical Subject Headings] ,Haplotype ,lcsh:RM1-950 ,Hepatotoxicity ,drug-induced liver injury,pharmacogenetics ,Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets [Medical Subject Headings] ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Antígenos HLA ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural [Medical Subject Headings] ,Pharmacogenetics ,Immunology ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Natural Killer Cell::Receptors, KIR [Medical Subject Headings] ,Enfermedad hepática inducida por drogas ,Genotipo ,030215 immunology - Abstract
Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development., The present study has been supported by grants of the Instituto de Salud Carlos III co-founded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI12/00378, SAS-PI-0239/2012, AC-0073-2013) and by the Agencia Española del Medicamento. CIBERehd is funded by Instituto de Salud Carlos III.
- Published
- 2016
66. Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury
- Author
-
Medina-Caliz, Inmaculada, Robles-Diaz, Mercedes, Garcia-Muñoz, Beatriz, Stephens, Camilla, Ortega-Alonso, Aida, Garcia-Cortes, Miren, González-Jimenez, Andres, Sanabria-Cabrera, Judith A, Moreno, Inmaculada, Fernandez, M Carmen, Romero-Gomez, Manuel, Navarro, Jose M, Barriocanal, Ana M, Montane, Eva, Hallal, Hacibe, Blanco, Sonia, Soriano, German, Roman, Eva M, Gómez-Dominguez, Elena, Castiella, Agustin, Zapata, Eva M, Jimenez-Perez, Miguel, Moreno, Jose M, Aldea-Perona, Ana, Hernández-Guerra, Manuel, Prieto, Martin, Zoubek, Miguel E, Kaplowitz, Neil, Lucena, M Isabel, Andrade, Raul J, and Spanish DILI registry
- Subjects
Drug ,medicine.medical_specialty ,Cirrhosis ,Bilirubin ,media_common.quotation_subject ,Disease ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Liver damage ,Prospective Studies ,Chronic ,Alanine aminotransferase ,media_common ,Liver injury ,Hepatology ,business.industry ,Hepatotoxicity ,Statins ,Alanine Transaminase ,medicine.disease ,Surgery ,Risk factors ,chemistry ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Chemical and Drug Induced Liver Injury ,business ,Dyslipidemia ,Follow-Up Studies - Abstract
Background & Aims: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. Methods: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or >= 1 year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. Results: Out of 298 patients enrolled 273 (92%) resolved 61 year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p = 0.011], dyslipidemia [OR: 4.26, p = 0.04] and severe DILI [OR: 14.22, p = 0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p < 0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. Conclusions: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. Lay summary: Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- Published
- 2016
67. Data Mining for Possible Drug-Host Interplay in Clinical Phenotypes of Drug-Induced Liver Injury
- Author
-
González-Jiménez, Andrés, primary, Chen, Minjun, additional, McEuen, Kristin, additional, Robles-diaz, Mercedes, additional, Medina-Caliz, Inmaculada, additional, Slim, Mahmoud, additional, Sanabria, Judith A., additional, Stephens, Camilla, additional, Lucena, Maria Isabel, additional, Andrade, Raul J., additional, and Suzuki, Ayako, additional
- Published
- 2017
- Full Text
- View/download PDF
68. Perfect PICNICS.
- Author
-
Stephens, Camilla, Randles, Annabelle, Sturdy, Carmen, and Rundle, Oana
- Published
- 2020
69. The influence of drug properties and host factors on delayed onset of symptoms in drug‐induced liver injury.
- Author
-
Gonzalez‐Jimenez, Andres, Robles‐Diaz, Mercedes, Medina‐Caliz, Inmaculada, Stephens, Camilla, Andrade, Raúl J., Lucena, M. Isabel, McEuen, Kristin, Chen, Minjun, Suzuki, Ayako, Bessone, Fernando, Hernandez, Nelia, Arrese, Marco, and Parana, Raymundo
- Subjects
SYMPTOMS ,LIVER injuries ,SMOKING cessation ,DRUG interactions ,ANTI-inflammatory agents ,HEART diseases - Abstract
Background & Aims: Most patients with drug‐induced liver injury (DILI) manifest clinical symptoms while on therapy, while some patients manifest days or weeks after drug cessation (delayed onset). This challenges DILI causality assessment and diagnosis. Factors contributing to the delayed onset phenotype are currently unknown. We explored factors contributing to delayed onset of DILI by analysing culprit drug properties, host factors and their interactions in a large patient population from the Spanish DILI Registry. Methods: Clinical information from 388 patients (69 presented delayed onset) and drug properties of 43 causative drugs (45 active ingredients) were analysed. A two‐tier regression‐based model was used to assess host/drug interactions affecting the probability of delayed onset. Results: Antibacterial and anti‐inflammatory drugs accounted for the delayed onset cases. Drug property of <50% hepatic metabolism (odds ratio [OR] 11.06, 95% confidence interval [95% CI]: 4.4‐32.2, P = 0.0003), daily dose ≥1000 mg (OR: 2.77, 95% CI: 1.3‐6.1, P = 0.0063) and the absence of pre‐existing conditions in a patient (OR: 2.55, 95% CI: 1.3‐4.9, P = 0.0043) were independently associated with delayed onset. The findings were consistent when externally validated using Latin American DILI Network cases (N = 131). Likewise, drug properties of mitochondrial liability and Pauling electronegativity were associated with delayed onset, but dependent on specific host factors such as age, sex and pre‐existing cardiac diseases. Conclusions: This study demonstrated that delayed onset, a specific DILI phenotype, is explained by complex interactions among drug properties and host factors and provided mechanistic hypotheses for future studies. These findings can help improve the diagnostic capability and causality assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
70. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate–Induced Liver Injury in Spanish Patients
- Author
-
Instituto de Salud Carlos III, European Commission, Agencia Española de Medicamentos y Productos Sanitarios, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Stephens, Camilla, Moreno-Casares, Antonia, López-Nevot, Miguel-Ángel, García-Cortés, Miren, Medina-Cáliz, Inmaculada, Hallal, Hacibe, Soriano, Germán, Román, Eva, Ruiz-Cabello, Francisco, Romero-Gómez, Manuel, Lucena, M. Isabel, Andrade, Raúl J., Instituto de Salud Carlos III, European Commission, Agencia Española de Medicamentos y Productos Sanitarios, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Stephens, Camilla, Moreno-Casares, Antonia, López-Nevot, Miguel-Ángel, García-Cortés, Miren, Medina-Cáliz, Inmaculada, Hallal, Hacibe, Soriano, Germán, Román, Eva, Ruiz-Cabello, Francisco, Romero-Gómez, Manuel, Lucena, M. Isabel, and Andrade, Raúl J.
- Abstract
Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand associatio
- Published
- 2016
71. Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort
- Author
-
Ulzurrun, Eugenia, Stephens, Camilla, Ruiz-Cabello, Francisco, Robles-Diaz, Mercedes, Saenz-López, Pablo, Hallal, Hacibe, Soriano, German, Roman, Eva, Fernandez, M. Carmen, Lucena, M. Isabel, Andrade, Raúl J., Universitat Autònoma de Barcelona, [Ulzurrun,E, Stephens,C, Robles-Díaz,M, Lucena,MI, Andrade, RJ] S Farmacología Clínica and UGC de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain. [Ulzurrun,E, Soriano,G, Román,E, Andrade, RJ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. [Ruiz-Cabello,F, Sáenz-López,P] Departamento de Bioquímica y Biología Molecular III/Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain. [Ruiz-Cabello,F] Instituto de Investigación Biosanitario de Granada, Spain. [Hallal,H] Servicio de Aparato Digestivo, Hospital Morales Meseguer, Murcia, Spain. [Soriano,G, Román,E] Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. [Román,E] Escola Universitària d'Infermeria EUI-Sant Pau, Universitat Autònoma de Barcelona, Spain. [Fernández,MC] Unidad de Gestión Clínica de Farmacia, Hospital Torrecárdenas, Almería, Spain., and This study was supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). CIBERehd and Red Genómica del Cáncer are funded by Instituto de Salud Carlos III.
- Subjects
Oncology ,Gerontology ,Male ,Linkage disequilibrium ,España ,lcsh:Medicine ,Genome-wide association study ,Linkage Disequilibrium ,Cohort Studies ,Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Bilirrubina ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Transport Proteins::ATP-Binding Cassette Transporters [Medical Subject Headings] ,Risk Factors ,Medicine and Health Sciences ,Bile ,Young adult ,lcsh:Science ,Aged, 80 and over ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Multidisciplinary ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Transport Proteins::ATP-Binding Cassette Transporters::Multidrug Resistance-Associated Proteins [Medical Subject Headings] ,Multidrug resistance-associated protein 2 ,Liver Diseases ,Homozygote ,Clinical Pharmacology ,Genomics ,ABCB4 ,Middle Aged ,Multidrug Resistance-Associated Protein 2 ,Research Design ,Cohort ,Female ,Drug therapy ,Haplotipos ,Chemical and Drug Induced Liver Injury ,Multidrug Resistance-Associated Proteins ,Alelos ,Drug induced hepatotoxicity ,Research Article ,Adult ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Adolescent ,Genotype ,Clinical Research Design ,Polimorfismo Genético ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Young Adult ,Pharmacotherapy ,Genomic Medicine ,Adverse Reactions ,Chemicals and Drugs::Biological Factors::Pigments, Biological::Bile Pigments::Bilirubin [Medical Subject Headings] ,Internal medicine ,medicine ,Genetics ,Humans ,Genetic Testing ,Variant genotypes ,Transportadoras de Casetes de Unión a ATP ,Proteínas Asociadas a Resistencia a Múltiples Medicamentos ,Genetic Association Studies ,Alleles ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] ,Aged ,Clinical Genetics ,Pharmacology ,Evolutionary Biology ,Drug metabolism ,Polymorphism, Genetic ,Enfermedad Hepática Inducida por Drogas ,business.industry ,Diseases::Substance-Related Disorders::Poisoning::Drug-Induced Liver Injury [Medical Subject Headings] ,lcsh:R ,Personalized Medicine ,Correction ,Biology and Life Sciences ,Human Genetics ,Bilirubin ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings] ,Estudios Epidemiológicos ,Haplotypes ,Spain ,Pharmacogenetics ,Genetic Polymorphism ,lcsh:Q ,Clinical Medicine ,business ,Population Genetics ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies [Medical Subject Headings] - Abstract
[Background and Aims] Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. [Methods] A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. [Results] None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. [Conclusions] Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility., This study was supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). CIBERehd and Red Genómica del Cáncer are funded by Instituto de Salud Carlos III.
- Published
- 2014
72. Chapter 18 - Causality Assessment
- Author
-
Lucena, M. Isabel, Stephens, Camilla, García-Cortés, Miren, and Andrade, Raúl J.
- Published
- 2013
- Full Text
- View/download PDF
73. Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis
- Author
-
Stephens, Camilla, primary, Castiella, Agustin, additional, Gomez-Moreno, Eva M., additional, Otazua, Pedro, additional, López-Nevot, Miguel-Ángel, additional, Zapata, Eva, additional, Ortega-Alonso, Aida, additional, Ruiz-Cabello, Francisco, additional, Medina-Cáliz, Inmaculada, additional, Robles-Díaz, Mercedes, additional, Soriano, German, additional, Roman, Eva, additional, Hallal, Hacibe, additional, Moreno-Planas, José M., additional, Prieto, Martin, additional, Andrade, Raúl J., additional, and Lucena, M. Isabel, additional
- Published
- 2016
- Full Text
- View/download PDF
74. Biomarkers in DILI: One More Step Forward
- Author
-
Robles-Díaz, Mercedes, primary, Medina-Caliz, Inmaculada, additional, Stephens, Camilla, additional, Andrade, Raúl J., additional, and Lucena, M. Isabel, additional
- Published
- 2016
- Full Text
- View/download PDF
75. Elevated levels of circulating CDH5 and FABP1 in association with human drug‐induced liver injury
- Author
-
Mikus, Maria, primary, Drobin, Kimi, additional, Gry, Marcus, additional, Bachmann, Julie, additional, Lindberg, Johan, additional, Yimer, Getnet, additional, Aklillu, Eleni, additional, Makonnen, Eyasu, additional, Aderaye, Getachew, additional, Roach, James, additional, Fier, Ian, additional, Kampf, Caroline, additional, Göpfert, Jens, additional, Perazzo, Hugo, additional, Poynard, Thierry, additional, Stephens, Camilla, additional, Andrade, Raúl J., additional, Lucena, M Isabel, additional, Arber, Nadir, additional, Uhlén, Mathias, additional, Watkins, Paul B., additional, Schwenk, Jochen M., additional, Nilsson, Peter, additional, and Schuppe‐Koistinen, Ina, additional
- Published
- 2016
- Full Text
- View/download PDF
76. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury
- Author
-
Ortega-Alonso, Aida, primary, Stephens, Camilla, additional, Lucena, M., additional, and Andrade, Raúl, additional
- Published
- 2016
- Full Text
- View/download PDF
77. On-the-go! Lunchtime RECIPES.
- Author
-
Stephens, Camilla, Watchers, Weight, and Hall, Maryanne
- Published
- 2019
78. Correction: Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort
- Author
-
Ulzurrun, Eugenia, primary, Stephens, Camilla, additional, Ruiz-Cabello, Francisco, additional, Robles-Diaz, Mercedes, additional, Saenz-López, Pablo, additional, Hallal, Hacibe, additional, Soriano, German, additional, Roman, Eva, additional, Fernandez, M. Carmen, additional, Lucena, M. Isabel, additional, and Andrade, Raúl J., additional
- Published
- 2015
- Full Text
- View/download PDF
79. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid‐responsive hepatitis: report of 22 cases
- Author
-
Bessone, Fernando, primary, Lucena, MI, additional, Roma, Marcelo G., additional, Stephens, Camilla, additional, Medina‐Cáliz, Inmaculada, additional, Frider, Bernardo, additional, Tsariktsian, Guillermo, additional, Hernández, Nelia, additional, Bruguera, Miquel, additional, Gualano, Gisela, additional, Fassio, Eduardo, additional, Montero, Joaquín, additional, Reggiardo, María V, additional, Ferretti, Sebastián, additional, Colombato, Luis, additional, Tanno, Federico, additional, Ferrer, Jaime, additional, Zeno, Lelio, additional, Tanno, Hugo, additional, and Andrade, Raúl J., additional
- Published
- 2015
- Full Text
- View/download PDF
80. Reply
- Author
-
Robles-Diaz, Mercedes, primary, Kaplowitz, Neil, additional, Stephens, Camilla, additional, Andrade, Raúl J., additional, and Lucena, M. Isabel, additional
- Published
- 2015
- Full Text
- View/download PDF
81. Reply
- Author
-
Robles-Diaz, Mercedes, primary, Kaplowitz, Neil, additional, Stephens, Camilla, additional, Andrade, Raul J., additional, and Lucena, M. Isabel, additional
- Published
- 2014
- Full Text
- View/download PDF
82. 1117 - Data Mining for Possible Drug-Host Interplay in Clinical Phenotypes of Drug-Induced Liver Injury
- Author
-
González-Jiménez, Andrés, Chen, Minjun, McEuen, Kristin, Robles-diaz, Mercedes, Medina-Caliz, Inmaculada, Slim, Mahmoud, Sanabria, Judith A., Stephens, Camilla, Lucena, Maria Isabel, Andrade, Raul J., and Suzuki, Ayako
- Published
- 2017
- Full Text
- View/download PDF
83. Mechanisms of drug-induced liver injury
- Author
-
Stephens, Camilla, primary, Andrade, Raúl J., additional, and Lucena, M. Isabel, additional
- Published
- 2014
- Full Text
- View/download PDF
84. Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury
- Author
-
Robles–Diaz, Mercedes, primary, Lucena, M. Isabel, additional, Kaplowitz, Neil, additional, Stephens, Camilla, additional, Medina–Cáliz, Inmaculada, additional, González–Jimenez, Andres, additional, Ulzurrun, Eugenia, additional, Gonzalez, Ana F., additional, Fernandez, M. Carmen, additional, Romero–Gómez, Manuel, additional, Jimenez–Perez, Miguel, additional, Bruguera, Miguel, additional, Prieto, Martín, additional, Bessone, Fernando, additional, Hernandez, Nelia, additional, Arrese, Marco, additional, and Andrade, Raúl J., additional
- Published
- 2014
- Full Text
- View/download PDF
85. HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity
- Author
-
Stephens, Camilla, primary, López-Nevot, Miguel-Ángel, additional, Ruiz-Cabello, Francisco, additional, Ulzurrun, Eugenia, additional, Soriano, Germán, additional, Romero-Gómez, Manuel, additional, Moreno-Casares, Antonia, additional, Lucena, M. Isabel, additional, and Andrade, Raúl J., additional
- Published
- 2013
- Full Text
- View/download PDF
86. CgDN24: A gene involved in hyphal development in the fungal phytopathogen Colletotrichum gloeosporioides
- Author
-
Stephenson, Sally-Anne, Stephens, Camilla, Maclean, Donald, Manners, John, Stephenson, Sally-Anne, Stephens, Camilla, Maclean, Donald, and Manners, John
- Abstract
A cDNA corresponding to a transcript induced in culture by N starvation, was identified in Colletotrichum gloeosporioides by a differential hybridisation strategy. The cDNA comprised 905 bp and predicted a 215 aa protein; the gene encoding the cDNA was termed CgDN24. No function for CgDN24 could be predicted by database homology searches using the cDNA sequence and no homologues were found in the sequenced fungal genomes. Transcripts of CgDN24 were detected in infected leaves of Stylosanthes guianensis at stages of infection that corresponded with symptom development. The CgDN24 gene was disrupted by homologous recombination and this led to reduced radial growth rates and the production of hyphae with a hyperbranching phenotype. Normal sporulation was observed, and following conidial inoculation of S. guianensis, normal disease development was obtained. These results demonstrate that CgDN24 is necessary for normal hyphal development in axenic culture but dispensable for phytopathogenicity. © 2005 Elsevier GmbH. All rights reserved.
- Published
- 2005
87. Building a Spanish-Latin American network on drug induced liver injury: much to get from a joint collaborative initiative
- Author
-
Bessone, Fernando, primary, Hernandez, Nelia, additional, Dávalos, Milagros, additional, Paraná, Raymundo, additional, Schinoni, María I., additional, Lizarzabal, Maribel, additional, Kershenobich, David, additional, Loaeza, Aurora, additional, Arrese, Marco, additional, Chirino, Ruby A., additional, Méndez-Sánchez, Nahum, additional, Fay, Fabian, additional, Bruguera, Miguel, additional, Stephens, Camilla, additional, Lucena, María I., additional, and Andrade, Raúl J., additional
- Published
- 2012
- Full Text
- View/download PDF
88. Trends in Qualifying Biomarkers in Drug Safety. Consensus of the 2011 Meeting of the Spanish Society of Clinical Pharmacology
- Author
-
Agúndez, José A. G., primary, del Barrio, Jaime, additional, Padró, Teresa, additional, Stephens, Camilla, additional, Farré, Magí, additional, Andrade, Raúl J., additional, Badimon, Lina, additional, García-Martín, Elena, additional, Vilahur, Gemma, additional, and Lucena, M. Isabel, additional
- Published
- 2012
- Full Text
- View/download PDF
89. Genetic variations in drug-induced liver injury (DILI): resolving the puzzle
- Author
-
Stephens, Camilla, primary, Lucena, M. Isabel, additional, and Andrade, Raúl J., additional
- Published
- 2012
- Full Text
- View/download PDF
90. Causality assessment methods in drug induced liver injury: Strengths and weaknesses
- Author
-
García-Cortés, Miren, primary, Stephens, Camilla, additional, Lucena, M. Isabel, additional, Fernández-Castañer, Alejandra, additional, and Andrade, Raúl J., additional
- Published
- 2011
- Full Text
- View/download PDF
91. Susceptibility to Amoxicillin-Clavulanate-Induced Liver Injury Is Influenced by Multiple HLA Class I and II Alleles
- Author
-
Lucena, M. Isabel, primary, Molokhia, Mariam, additional, Shen, Yufeng, additional, Urban, Thomas J., additional, Aithal, Guruprasad P., additional, Andrade, Raúl J., additional, Day, Christopher P., additional, Ruiz–Cabello, Francisco, additional, Donaldson, Peter T., additional, Stephens, Camilla, additional, Pirmohamed, Munir, additional, Romero–Gomez, Manuel, additional, Navarro, Jose Maria, additional, Fontana, Robert J., additional, Miller, Michael, additional, Groome, Max, additional, Bondon–Guitton, Emmanuelle, additional, Conforti, Anita, additional, Stricker, Bruno H.C., additional, Carvajal, Alfonso, additional, Ibanez, Luisa, additional, Yue, Qun–Ying, additional, Eichelbaum, Michel, additional, Floratos, Aris, additional, Pe'er, Itsik, additional, Daly, Mark J., additional, Goldstein, David B., additional, Dillon, John F., additional, Nelson, Matthew R., additional, Watkins, Paul B., additional, and Daly, Ann K., additional
- Published
- 2011
- Full Text
- View/download PDF
92. Hepatotoxicidad, un problema global con especificidades locales: hacia la creación de una Red Hispano Latinoamericana de Hepatotoxicidad
- Author
-
Lucena, María Isabel, primary, Cohen, Henry, additional, Hernández, Nelia, additional, Bessone, Fernando, additional, Dacoll, Cristina, additional, Stephens, Camilla, additional, Borraz, Yolanda, additional, Ulzurrun, Eugenia, additional, Bruguera, Miguel, additional, and Andrade, Raúl J., additional
- Published
- 2011
- Full Text
- View/download PDF
93. CgDN24: A gene involved in hyphal development in the fungal phytopathogen Colletotrichum gloeosporioides
- Author
-
Stephenson, Sally-Anne, primary, Stephens, Camilla M., additional, Maclean, Donald J., additional, and Manners, John M., additional
- Published
- 2005
- Full Text
- View/download PDF
94. The mode of action of the plant antimicrobial peptide MiAMP1 differs from that of its structural homologue, the yeast killer toxin WmKT
- Author
-
Stephens, Camilla, primary, Kazan, Kemal, additional, Goulter, Ken C., additional, Maclean, Donald J., additional, and Manners, John M., additional
- Published
- 2005
- Full Text
- View/download PDF
95. Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort.
- Author
-
Ulzurrun, Eugenia, Stephens, Camilla, Ruiz-Cabello, Francisco, Robles-Diaz, Mercedes, Saenz-López, Pablo, Hallal, Hacibe, Soriano, German, Roman, Eva, Fernandez, M. Carmen, Lucena, M. Isabel, and Andrade, Raúl J.
- Subjects
- *
LIVER injuries , *THERAPEUTICS , *GENETIC polymorphisms , *HEPATOTOXICOLOGY , *GASTROENTEROLOGY , *PHARMACOGENOMICS , *INDIVIDUALIZED medicine - Abstract
Background and Aims: Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. Methods: A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. Results: None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. Conclusions: Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
96. Higgidy roasted risotto pumpkin pie.
- Author
-
Stephens, Camilla
- Published
- 2019
97. Pesto roasted squash.
- Author
-
Stephens, Camilla
- Published
- 2019
98. Pumpkin pecan pie.
- Author
-
Stephens, Camilla
- Published
- 2019
99. Roasted pumpkin and blue cheese lasagne.
- Author
-
Stephens, Camilla
- Published
- 2019
100. Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study
- Author
-
Watkins, Paul B., Urban, Thomas J., Nelson, Matthew R., Shen, Yufeng, Day, Christopher P., Larrey, Dominique, Hallberg, Pär, Nicoletti, Paola, Stephens, Camilla, Grove, Jane I., Fontana, Robert J., Cascorbi, Ingolf, Daly, Ann K., Aithal, Guruprasad P., Bessone, Fernando, Molokhia, Mariam, Sawle, Ashley, Arrese, Marco, Floratos, Aris, Conforti, Anita, Hayashi, Paul H., Chalasani, Naga, Barnhart, Huiman X., Daly, Mark J., Dillon, John F., Hernández, Nelia, Ibáñez, Luisa, Laitinen, Tarja, Qin, Shengying, Kullak-Ublick, Gerd A., Wadelius, Mia, Andrade, Raul J., Maitland-van der Zee, Anke H., Stolz, Andrew, Serrano, Jose, Coulthard, Sally A., Bondon-Guitton, Emmanuelle, Pirmohamed, Munir, Bjornsson, Einar S., Martin, Jennifer H., Powell, Elizabeth E., Lucena, M. Isabel, Carvajal, Alfonso, and Cirulli, Elizabeth T.
- Subjects
3. Good health - Abstract
BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9-3.8; P = 2.4 × 10-8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6-2.5; P = 9.7 × 10-9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6-2.7; P = 4.8 × 10-9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0-9.5; P = 7.1 × 10-9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.