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1. Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.

Author

Simone Bocchetta, Patrick Maillard, Mami Yamamoto, Claire Gondeau, Florian Douam, Stéphanie Lebreton, Sylvie Lagaye, Stanislas Pol, François Helle, Wanee Plengpanich, Maryse Guérin, Maryline Bourgine, Marie Louise Michel, Dimitri Lavillette, Philippe Roingeard, Wilfried le Goff, and Agata Budkowska

Subjects
Medicine, Science
Abstract

Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy.

Published
2014
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3. Il paese dei re

Author

Simone Bocchetta, Giulia Vannutelli

Published
2020

8. HL-370 Fragmentóme Profiling Reveals Distinct Molecular Subgroups of Classic Hodgkin Lymphoma

Author

Lodovico Terzi di Bergamo, Maria Cristina Pirosa, Alessio Bruscaggin, Matin Salehi, Valeria Spina, Katia Pini, Simone Bocchetta, Claudia Giordano, Adalgisa Condouci, Gabriela Forestieri, Deborah Piffaretti, Joyce Marques de Almeida, Salvatore Annunziata, Fabrizio Bergesio, Eugenio Borsatti, Pietro Bulian, Stephane Chauvie, Marco Cuzzocrea, Martina Di Trani, Bernhard Gerber, Michal Kurlapski, Alden Moccia, Riccardo Moia, Andrea Rinaldi, Marcello Rodari, Grzegorz Romanowicz, Gian Mauro Sacchetti, Alessandra Stasia, Anastasios Stathis, Georg Stuessi, Ilaria Zangrilli, Luigi Maria Larocca, Antonello Pinto, Armando Santoro, Franco Cavalli, Emanuele Zucca, Valter Gattei, Jan Maciej Zaucha, Carmelo Carlo Stella, Stefan Hohaus, Gianluca Gaidano, Luca Ceriani, and Davide Rossi

Subjects
Cancer Research, Oncology, Hematology
Published
2022
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9. Poster: HL-370 Fragmentome Profiling Reveals Distinct Molecular Subgroups of Classic Hodgkin Lymphoma

Author

Lodovico Terzi di Bergamo, Maria Cristina Pirosa, Alessio Bruscaggin, Matin Salehi, Valeria Spina, Katia Pini, Simone Bocchetta, Claudia Giordano, Adalgisa Condouci, Gabriela Forestieri, Deborah Piffaretti, Joyce Marques de Almeida, Salvatore Annunziata, Fabrizio Bergesio, Eugenio Borsatti, Pietro Bulian, Stephane Chauvie, Marco Cuzzocrea, Martina Di Trani, Bernhard Gerber, Michal Kurlapski, Alden Moccia, Riccardo Moia, Andrea Rinaldi, Marcello Rodari, Grzegorz Romanowicz, Gian Mauro Sacchetti, Alessandra Stasia, Anastasios Stathis, Georg Stuessi, Ilaria Zangrilli, Luigi Maria Larocca, Antonello Pinto, Armando Santoro, Franco Cavalli, Emanuele Zucca, Valter Gattei, Jan Maciej Zaucha, Carmelo Carlo Stella, Stefan Hohaus, Gianluca Gaidano, Luca Ceriani, and Davide Rossi

Subjects
Cancer Research, Oncology, Hematology
Published
2022
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10. Recent advances in HCV entry

Author

Michela Emma Burlone, Mario Pirisi, Simone Bocchetta, Andrea Magri, and Rosalba Minisini

Subjects
chemistry.chemical_classification, chemistry, In vivo, Mechanism (biology), Viral entry, Virology, LDL receptor, Transferrin receptor, Biology, Glycoprotein, Receptor, CD81
Abstract

ABSTRACT: The elucidation of the mechanisms by which HCV infects hepatocytes and replicates has been paramount for identifying therapeutic targets and developing the highly efficacious antiviral drugs from which we benefit today. The earliest stage of HCV infection is viral entry, a process in which a complex interplay is thought to occur between host molecules (including glycosaminoglycans, low-density lipoprotein receptor, CD81, SR-B1, CLDN1, OCLN, EGF receptor, ephrin type A receptor 2 and transferrin receptor 1) and envelope viral glycoproteins E1 and E2. The wealth of experimental data produced in the field of HCV entry is summarized in a proposed mechanism, updated to include the most recently published data on the topic. Compounds with putative entry-blocking and/or entry-inhibiting activity in vitro and in vivo are also briefly reviewed.

Published
2014
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11. Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection

Author

Claire Gondeau, Simone Bocchetta, François Helle, Philippe Roingeard, Florian Douam, Wanee Plengpanich, Agata Budkowska, Maryse Guerin, Stanislas Pol, Sylvie Lagaye, Dimitri Lavillette, Marie Michel, Stéphanie Lebreton, Wilfried Le Goff, Patrick Maillard, Maryline Bourgine, Mami Yamamoto, Hépacivirus et Immunité innée, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Medicina Translazionale, Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Department of Biochemistry, Nihon University School of Medicine, Nihon University-Nihon University, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Trafic membranaire et Pathogénèse, Institut Pasteur [Paris] (IP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Dyslipidémies, inflammation et athérosclérose dans les maladies métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenèse des Virus de l'Hépatite B (PVHB), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Institut Pasteur [Paris], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Università degli Studi del Piemonte Orientale-Amedeo Avogadro (ITALY), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Universita ' del Piemonte Orientale, 'Amedeo Avogadro', Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogenèse des Virus de l'Hépatite B ( PVHB ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Morphogénèse et antigénicité du VIH et du virus des Hépatites ( MAVIVH ), Université de Tours-CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Benzylamines, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, lcsh:Medicine, Pathogenesis, Hepacivirus, [ SDV.BA ] Life Sciences [q-bio]/Animal biology, Pathology and Laboratory Medicine, Virus Replication, Benzoates, Cell Fusion, chemistry.chemical_compound, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Cell Biology, Medicine and Health Sciences, ABCA1 Gene, lcsh:Science, Lipid raft, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, Cell fusion, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Antimicrobials, [SDV.BA]Life Sciences [q-bio]/Animal biology, Cell Cycle, Antivirals, Hepatitis C, Up-Regulation, 3. Good health, Cell biology, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cholesterol, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, Biochemistry, Medical Microbiology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Host-Pathogen Interactions, RNA, Viral, Receptors, Virus, lipids (amino acids, peptides, and proteins), Research Article, ATP Binding Cassette Transporter 1, Virus Attachment, Gastroenterology and Hepatology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Microbiology, [ SDV.EE ] Life Sciences [q-bio]/Ecology, environment, Membrane Microdomains, Viral entry, Microbial Control, Virology, Cell Line, Tumor, Humans, Secretion, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Liver X receptor, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Microbial Pathogens, [ SDV.BID ] Life Sciences [q-bio]/Biodiversity, lcsh:R, Virion, Biology and Life Sciences, Cell Biology, Virus Internalization, Lipid Metabolism, HEK293 Cells, chemistry, ABCA1, Hepatocytes, biology.protein, lcsh:Q
Abstract

International audience; Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy.

Published
2014
Full Text
View/download PDF

12. Fibrosis progression in HCV carriers with mild hepatitis who possess the high-repetition variant of the DRD4 gene, a genetic marker for binge-drinking and risk-seeking behavior: a longitudinal study

Author

C. Colletta, Mario Pirisi, Simone Bocchetta, Alessandro Colletta, Emanuele Alaimo, E. Boccato, Rosalba Minisini, Carlo Smirne, Serena Favretto, Carmen Vandelli, and Michela Emma Burlone

Subjects
Liver Cirrhosis, medicine.medical_specialty, Pathology, Alcohol Drinking, Biopsy, Medicine (miscellaneous), Binge drinking, Minisatellite Repeats, Biology, Toxicology, Gastroenterology, Severity of Illness Index, Binge Drinking, Cohort Studies, Risk-Taking, Gene Frequency, Risk Factors, Internal medicine, Receptors, medicine, Dopamine D4, Case-Control Studies, Disease Progression, Hepatitis C, Chronic, Longitudinal Studies, Multivariate Analysis, Receptors, Dopamine D4, Self Report, Chronic, Allele frequency, Hepatitis, medicine.diagnostic_test, Hepatitis C, medicine.disease, Psychiatry and Mental health, Liver biopsy, Cohort, Body mass index, Viral load
Abstract

Background Alcohol is a major determinant of the outcome of chronic hepatitis C virus (HCV) infection, but self-reported drinking habits lack reliability. We hypothesized that carriage of high-repetition variants (HRV) of the variable number of tandem repeats (VNTR) in exon III of the dopamine receptor D4 gene, linked to binge-drinking and risk-seeking behavior, might be a proxy measure of alcohol consumption, and aimed to verify whether it may affect histologic outcome. Methods A cohort of HCV patients with normal or near-normal aminotransferases (N = 128) underwent a liver biopsy as part of diagnostic work-up. None admitted to exceed low-risk alcohol consumption; most (90/128, 70%) described themselves as teetotalers. They received advice on abstaining from alcohol, but not antiviral treatment. After a median follow-up period of 10 years, all underwent a second liver biopsy. HRV allele frequencies were compared with those of a group of healthy blood donors (N = 128) and related to liver histology. Results HRV allele frequencies were 0.19 in patients and 0.16 in controls (p = 0.182). In the subgroup of patients who admittedly had consumed alcohol, 20/38 (53%) carried HRV, in comparison with 27/90 patients (30%) who had denied to consume alcohol (p = 0.026 by Fisher's exact test). Carriage of HRV was associated with higher histologic grade (p = 0.002) and stage (p = 0.009) at the final biopsy. At multivariate analysis, among a set of variables also including viral genotype, viral load, body mass index, gender, and history of alcohol consumption, only age (OR = 1.06, 95% CI 1.02 to 1.11) and HRV (OR = 3.13, 95% CI 1.28 to 7.68) were independent predictors of significant fibrosis at the end of follow-up. Conclusions The link between HRV carriage and histologic outcome in a subgroup of HCV patients at low risk of progression underlines the need for intense scrutiny of alcohol habits in hepatitis C.

Published
2013

13. JAK2V617F in idiopathic venous thromboembolism occurring in the absence of inherited or acquired thrombophilia

Author

Monia Lunghi, Davide Rossi, Tamara Destro, Stefania Cresta, Chiara Vendramin, Lorenzo De Paoli, Michaela Cerri, Simone Bocchetta, and Gianluca Gaidano

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Thrombophilia, Thromboembolism, Internal medicine, Coagulopathy, Humans, Medicine, Aged, business.industry, Vascular disease, Acquired thrombophilia, Hematology, Janus Kinase 2, Middle Aged, medicine.disease, Pulmonary embolism, JAK2 Protein Tyrosine Kinase, Venous thrombosis, Mutation, Cardiology, Female, Pulmonary Embolism, business, Venous thromboembolism
Published
2007
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14. Albert Camus

Author

Simone Bocchetta, Massimo Borghesi, Simone Bocchetta, Simone Bocchetta, Massimo Borghesi, and Simone Bocchetta

Abstract

A sessant’anni dalla morte

15. Studium nella storia

Author

Simone Bocchetta, Vincenzo Cappelletti, Simone Bocchetta, Simone Bocchetta, Vincenzo Cappelletti, and Simone Bocchetta

Abstract

Il primo Convegno culturale di Studium

16. Albert Camus

Author

Simone Bocchetta, Massimo Borghesi, Simone Bocchetta, Simone Bocchetta, Massimo Borghesi, and Simone Bocchetta

Abstract

A sessant’anni dalla morte

17. Studium nella storia

Author

Simone Bocchetta, Vincenzo Cappelletti, Simone Bocchetta, Simone Bocchetta, Vincenzo Cappelletti, and Simone Bocchetta

Abstract

Il primo Convegno culturale di Studium

18. Albert Camus

Author

Simone Bocchetta, Massimo Borghesi, Simone Bocchetta, Simone Bocchetta, Massimo Borghesi, and Simone Bocchetta

Abstract

A sessant’anni dalla morte

19. Studium nella storia

Author

Simone Bocchetta, Vincenzo Cappelletti, Simone Bocchetta, Simone Bocchetta, Vincenzo Cappelletti, and Simone Bocchetta

Abstract

Il primo Convegno culturale di Studium

20. Albert Camus

Author

Simone Bocchetta, Massimo Borghesi, Simone Bocchetta, Simone Bocchetta, Massimo Borghesi, and Simone Bocchetta

Abstract

A sessant’anni dalla morte

21. Studium nella storia

Author

Simone Bocchetta, Vincenzo Cappelletti, Simone Bocchetta, Simone Bocchetta, Vincenzo Cappelletti, and Simone Bocchetta

Abstract

Il primo Convegno culturale di Studium

22. IL28B polymorphism, blood interferon-alpha concentration, and disease stage of HCV mono-infected and HCV-HIV co-infected patients

Author

E. Boccato, Olivia Bargiacchi, Mario Pirisi, G. Occhino, Rosalba Minisini, Simone Bocchetta, Michela Emma Burlone, Giovanni Rizzo, Andrea Cerutti, E. Ceriani, and Carlo Smirne

Subjects
Liver Cirrhosis, Male, Genotype, Renal function, Alpha interferon, HIV Infections, Interferon, Virology, medicine, Humans, Retrospective Studies, Polymorphism, Genetic, business.industry, Coinfection, Interleukins, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Infectious Diseases, Immunology, Population study, Elasticity Imaging Techniques, Female, Interferons, Transient elastography, business, Biomarkers, medicine.drug
Abstract

Interferon (IFN) preactivation, interleukin-28B (IL28B) alleles, and liver fibrosis act as predictors of response to antiviral therapy against hepatitis C. We aimed to verify if blood IFN concentration, a putative biomarker of interferon preactivation, might depend on carriage of a given IL28B genotype and/or advanced hepatic fibrosis. The study population included 187 hepatitis C patients (75 of whom were HIV coinfected), who were genotyped for the rs12979860 polymorphism and staged non-invasively by transient elastography. Blood IFN, measured by an enzyme immunoassay, was detectable in 68/187 patients (36%). Seventy-three patients (39%) were C/C homozygotes, 25 (13%) were T/T homozygotes, and 89 (48%) were heterozygotes. The fibrosis stage was F0-F1 in 70 patients (37%), F2-F3 in 54 patients (29%), and F4 in 63 patients (34%). IFN levels were higher among patients with HIV coinfection (p=0.044) and patients with better renal function (p=0.041), without association with the IL28B genotype or the hepatitis C stage. From the multivariate analysis, the only independent predictor of higher level of IFN was the age of patients (p=0.019), whereas independent predictors of a fibrosis stage ≥ F2 were age (p=0.007), belonging to the HIV/HCV group (p=0.048) and current alcohol consumption (p=0.008). In conclusion, a sizable proportion of HCV carriers have detectable IFN levels that do not indicate a greater severity of disease or display any relationships to specific rs12979860 variants.

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