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1. Effect of Hepatitis E Virus RNA Universal Blood Donor Screening, Catalonia, Spain, 2017‒2020

Author

Marta Bes, Maria I. Costafreda, Mar Riveiro-Barciela, Maria Piron, Angie Rico, Josep Quer, Lluis Puig, and Silvia Sauleda

Subjects
hepatitis E virus, HEV, viruses, virus RNA, viral load, universal blood donor screening, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA–positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons.

Published
2022
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2. Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.

Author

Meritxell Llorens-Revull, Maria Isabel Costafreda, Angie Rico, Mercedes Guerrero-Murillo, Maria Eugenia Soria, Sofía Píriz-Ruzo, Elena Vargas-Accarino, Pablo Gabriel-Medina, Francisco Rodríguez-Frías, Mar Riveiro-Barciela, Celia Perales, Josep Quer, Silvia Sauleda, Juan Ignacio Esteban, and Marta Bes

Subjects
Medicine, Science
Abstract

Background & aimsHCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV.MethodsWe analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays.ResultsWe observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies.ConclusionsOur results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA's therapies.

Published
2021
Full Text
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3. Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Author

Maria Isabel Costafreda, Mar Riveiro-Barciela, Silvia Sauleda, Sofía Píriz-Ruzo, Celia Perales, Meritxell Llorens-Revull, Juan Ignacio Esteban, Francisco Rodriguez-Frias, María Eugenia Soria, Pablo Gabriel-Medina, Mercedes Guerrero-Murillo, Josep Quer, Marta Bes, Angie Rico, Elena Vargas-Accarino, Instituto de Salud Carlos III, Institut Català de la Salut, [Llorens-Revull M, Quer J] Laboratori d'Hepatitis Viral-Malalties Hepàtiques, Unitat del Fetge, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Costafreda MI] Laboratori d'Hepatitis Viral-Malalties Hepàtiques, Unitat del Fetge, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Transfusion Safety Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain. [Rico A] Laboratori d'Hepatitis Viral-Malalties Hepàtiques, Unitat del Fetge, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Transfusion Safety Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain. [Guerrero-Murillo M, Píriz-Ruzo S, Vargas-Accarino E] Laboratori d'Hepatitis Viral-Malalties Hepàtiques, Unitat del Fetge, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Soria ME] Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Campus de Cantoblanco, Madrid, Spain. Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain. [Gabriel-Medina P] Unitat de Patologia Hepàtica, Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rodríguez-Frías F] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat de Patologia Hepàtica, Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Bioquímica Clínica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Riveiro-Barciela M] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Unitat del Fetge, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Esteban JI] Laboratori d'Hepatitis Viral-Malalties Hepàtiques, Unitat del Fetge, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat del Fetge, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, RNA viruses, CD4-Positive T-Lymphocytes, Physiology, Cancer Treatment, enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis C crónica [ENFERMEDADES], Hepacivirus, CD8-Positive T-Lymphocytes, White Blood Cells, 0302 clinical medicine, Resposta immunitària, Animal Cells, Immune Physiology, Medicine and Health Sciences, Other subheadings::/therapeutic use [Other subheadings], Immune Response, Medicaments antivírics - Ús terapèutic - Eficàcia, Pathology and laboratory medicine, Otros calificadores::/terapia [Otros calificadores], Innate Immune System, Multidisciplinary, Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis C, Chronic [DISEASES], medicine.diagnostic_test, T Cells, Hepatitis C virus, ELISPOT, Liver Diseases, virus diseases, Hepatitis C, Hepatitis crònica activa, Medical microbiology, Middle Aged, Phenotype, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents [CHEMICALS AND DRUGS], medicine.anatomical_structure, Oncology, Viruses, Liver Fibrosis, Cytokines, Medicine, 030211 gastroenterology & hepatology, Cellular Types, Pathogens, Research Article, Adult, T cell, Immune Cells, Science, Immunology, Reversion, Cytotoxic T cells, Cytokine Therapy, Gastroenterology and Hepatology, Microbiology, Antiviral Agents, Flow cytometry, 03 medical and health sciences, Immune system, medicine, Humans, Immune response, Blood Cells, Flaviviruses, business.industry, Otros calificadores::/uso terapéutico [Otros calificadores], Organisms, Viral pathogens, Biology and Life Sciences, Cell Biology, Other subheadings::/therapy [Other subheadings], Molecular Development, Hepatitis C, Chronic, medicine.disease, Fibrosis, Hepatitis viruses, digestive system diseases, Microbial pathogens, 030104 developmental biology, Immune System, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos [COMPUESTOS QUÍMICOS Y DROGAS], business, Hepatitis C - Tractament, CD8, Developmental Biology
Abstract

Background & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-γ ELISPOT, intracellular cytokine staining (IL-2 and IFN-γ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-γ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies., Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (ERDF): grant numbers PI16/00337, PI18/00210 and PI19/00301. C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CP14/00121 and CPII19/00001) cofinanced by the European Regional Development Fund (ERDF)

Published
2021

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