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1. Strategies to manage hepatitis C virus (HCV) disease burden

Author

William Sievert, Wolfgang Vogel, C. E. Brandão Mello, Maria Lucia Gomes Ferraz, José Giria, Chris Estes, Homie Razavi, Martin Kåberg, Morris Sherman, Gamal Shiha, Christoph Sarrazin, Johannes Wiegand, J Parkes, Stephen D. Ryder, Filipe Calinas, Jan Sperl, Kevork M. Peltekian, Markus Cornberg, Matthew E. Cramp, Karolin Falconer, Marc Bilodeau, P. Van Damme, Anne Øvrehus, Philip Bruggmann, Maria Buti, Jose Luis Calleja, H. Van Vlierberghe, J. Félix, Achim Kautz, Jan Gerstoft, Peer Brehm Christensen, Gregory J. Dore, Necati Örmeci, Petr Urbánek, Kelly Kaita, N. Reis, Alexander J. Thompson, Javier García-Samaniego, Fernando L. Gonçales, Thomas Berg, S. Frankova, E. Gower, Amany Zekry, Peter Stärkel, Daniel Lavanchy, Florian Bihl, Beat Müllhaupt, Rui Tato Marinho, M. C. Mendes Correa, Pablo Lázaro, Françoise Roudot-Thoraval, Mette Rye Clausen, Vratislav Nemecek, Mel Krajden, Ulus Salih Akarca, İsmail Balik, Wim Laleman, Stuart K. Roberts, S. Mauss, Robert P. Myers, Michael Gschwantler, Wahid Doss, Sabahattin Kaymakoglu, Imam Waked, Hugo Cheinquer, Ayman Yosry, Gül Ergör, Ann-Sofi Duberg, Alnoor Ramji, Henrique Sérgio Moraes Coelho, H. Wedemeyer, Christophe Moreno, Christophe Hézode, Francesco Negro, S. J. Hindman, Henrik Krarup, Dominique Vandijck, I. van Thiel, Gamal Esmat, M Guimarães Pessôa, Manal H El-Sayed, Nina Weis, Paul Marotta, Antonio Javier Blasco, Ramazan Idilman, Rui Sarmento-Castro, Harald Hofer, Paulo R. Ferreira, David Semela, Rudolf E. Stauber, Petr Husa, Soo Aleman, William Rosenberg, Hannover Med Sch, German Liver Fdn, Orebro Univ Hosp, Univ Orebro, Hosp Valle de Hebron, UCL, Inst Clin & Expt Med, Cairo Univ, Ankara Univ, Ghent Univ Hosp, Wilhelminenspital Stadt Wien, Ege Univ, Karolinska Inst, Karolinska Univ Hosp, Univ Leipzig, Osped Cantonale, Univ Montreal, Adv Tech Hlth Serv Res TAISS, Fed Univ State Rio de Janeiro, Arud Ctr Addict Med, Hosp Santo Antonio Capuchos, Hosp Puerta Hierro, Univ Fed Rio Grande do Sul, Odense Univ Hosp, Region Hosp Hovedstaden, Universidade Federal do Rio de Janeiro (UFRJ), Univ Plymouth, Univ New S Wales, Ain Shams Univ, Dokuz Eylul Univ, Ctr Dis Anal CDA, Exigo Consultores, Universidade Federal de São Paulo (UNIFESP), Hosp Carlos III, Univ Copenhagen, Direccao Geral Saude, Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo (USP), Hop Henri Mondor, Med Univ Vienna, Masaryk Univ, Univ Manitoba, Hlth Sci Ctr, European Liver Patients Assoc, Istanbul Univ, Univ British Columbia, Aalborg Univ Hosp, Katholieke Univ Leuven, Univ Western Ontario, Univ Dusseldorf, Univ Libre Brussels, Univ Zurich Hosp, Univ Calgary, Natl Inst Publ Hlth, Univ Southhampton, Dalhousie Univ & Hepatol Serv, Assembleia Republ, Alfred Hosp, Monash Univ, Nottingham Univ Hosp NHS Trust, Biomed Res Unit, Ctr Hosp Porto, JW Goethe Univ Hosp, Cantonal Hosp St Gallen, Univ Toronto, Egyptian Liver Res Inst & Hosp ELRIAH, Catholic Univ Louvain, Med Univ Graz, St Vincents Hosp, Univ Melbourne, Charles Univ Prague, Cent Mil Hosp, Univ Antwerp, Deutsch Leberhilfe eV, Univ Ghent, Hasselt Univ, Med Univ Innsbruck, Natl Liver Inst, Copenhagen Univ Hosp, Univ Hosp, Monash Hlth, Bihl, Florian, Semela, David, and Negro, Francesco

Subjects
medicine.medical_specialty, diagnosis, Hepatitis C virus, Population, prevalence, ddc:616.07, medicine.disease_cause, law.invention, Telaprevir, disease burden, 03 medical and health sciences, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Randomized controlled trial, law, Virology, Internal medicine, medicine, 030212 general & internal medicine, education, Disease burden, ddc:616, education.field_of_study, Hepatology, treatment, business.industry, Ribavirin, scenarios, Hepatitis C, medicine.disease, mortality, 3. Good health, Infectious Diseases, chemistry, HCV, incidence, 030211 gastroenterology & hepatology, epidemiology, Human medicine, hepatitis C, business, medicine.drug
Abstract

Gilead Sciences The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. the largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical. Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany German Liver Fdn, Hannover, Germany Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Hosp Valle de Hebron, CIBERehd, Barcelona, Spain UCL, Div Med, UCL Inst Liver & Digest Hlth, London, England Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Cairo Univ, Cairo, Egypt Ankara Univ, TR-06100 Ankara, Turkey Ghent Univ Hosp, Ghent, Belgium Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Ege Univ, Izmir, Turkey Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Univ Leipzig, D-04109 Leipzig, Germany Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Adv Tech Hlth Serv Res TAISS, Madrid, Spain Fed Univ State Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Arud Ctr Addict Med, Zurich, Switzerland Hosp Santo Antonio Capuchos, Ctr Hosp Lisboa Cent, Dept Gastroenterol, Lisbon, Portugal Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Region Hosp Hovedstaden, Region Hovedstaden, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Ctr Dis Anal CDA, Louisville, CO USA Karolinska Inst, Dept Med Huddinge, Karolinska Univ Hosp, Infect Dis Unit, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Fac Ciencias Med, Disciplina Doencas Infecciosas, Grp Estudo Hepatites,Dept Clin Med, São Paulo, Brazil Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria Masaryk Univ, Clin Infect Dis, Univ Hosp Brno, Brno, Czech Republic Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ São Paulo, Sch Med, São Paulo, Brazil Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Univ Calgary, Div Gastroenterol & Hepatol, Liver Unit, Calgary, AB, Canada Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ & Hepatol Serv, Queen Elizabeth II Hlth Sci Ctr, Capital Dist Hlth Author, Dept Med, Halifax, NS, Canada Dalhousie Univ & Hepatol Serv, Queen Elizabeth II Hlth Sci Ctr, Capital Dist Hlth Author, Dept Surg, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal JW Goethe Univ Hosp, Frankfurt, Germany Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Egyptian Liver Res Inst & Hosp ELRIAH, Dakahliah, Egypt Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Univ Antwerp, B-2020 Antwerp, Belgium Deutsch Leberhilfe eV, Cologne, Germany Univ Ghent, Dept Hlth Econ & Patient Safety, B-9000 Ghent, Belgium Hasselt Univ, Diepenbeek, Belgium Med Univ Innsbruck, A-6020 Innsbruck, Austria Natl Liver Inst, Menoufia, Egypt Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Monash Hlth, Melbourne, Vic, Australia Division of Gastroenterology, Federal University of São Paulo, São Paulo, Brazil Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil Web of Science

Published
2014

2. Historical epidemiology of hepatitis C virus (HCV) in selected countries

Author

Markus Cornberg, Mette Rye Clausen, Marc Bilodeau, Wahid Doss, E. Gower, Karolin Falconer, Pablo Lázaro, Necati Örmeci, Beat Müllhaupt, Jose Luis Calleja, S. J. Hindman, Wim Laleman, Peer Brehm Christensen, J Parkes, Matthew E. Cramp, Anne Øvrehus, Vratislav Nemecek, Ulus Salih Akarca, Javier García-Samaniego, Sabahattin Kaymakoglu, Christophe Hézode, Jan Sperl, N. Reis, Heiner Wedemeyer, M. C. Mendes Correa, D. Vandijck, Morris Sherman, William Rosenberg, Henrique Sérgio Moraes Coelho, Alexander J. Thompson, Rudolf E. Stauber, Peter Stärkel, Maria Buti, M Guimarães Pessôa, William Sievert, Petr Husa, Wolfgang Vogel, Manal H El-Sayed, Robert P. Myers, Gamal Esmat, İsmail Balik, Fernando L. Gonçales, Francesco Negro, Petr Urbánek, Johannes Wiegand, Martin Kåberg, Christophe Moreno, Kevork M. Peltekian, Ramazan Idilman, S. Mauss, Soo Aleman, José Giria, Chris Estes, Gül Ergör, Ann-Sofi Duberg, Stuart K. Roberts, Nina Weis, Daniel Lavanchy, Kelly Kaita, Michael Gschwantler, Stephen D. Ryder, Hugo Cheinquer, Imam Waked, Ayman Yosry, Antonio Javier Blasco, Jan Gerstoft, Filipe Calinas, Paul Marotta, J. Félix, Henrik Krarup, Maria Lucia Gomes Ferraz, Homie Razavi, Gamal Shiha, Rui Tato Marinho, Christoph Sarrazin, Rui Sarmento-Castro, P. Van Damme, Mel Krajden, Achim Kautz, Harald Hofer, Florian Bihl, Gregory J. Dore, Thomas Berg, Amany Zekry, C. E. Brandão Mello, Alnoor Ramji, I. van Thiel, Paulo R. Ferreira, David Semela, Philip Bruggmann, S. Frankova, H. Van Vlierberghe, Françoise Roudot-Thoraval, Arud Ctr Addict Med, Univ Leipzig, Odense Univ Hosp, Univ Libre Brussels, Universidade Federal do Rio de Janeiro (UFRJ), Hop Henri Mondor, Hosp Santa Maria, Univ Toronto, Nottingham Univ Hosp NHS Trust, Biomed Res Unit, Inst Clin & Expt Med, Ege Univ, Ankara Univ, Osped Cantonale, Univ Montreal, Adv Tech Hlth Serv Res TAISS, Hosp Valle de Hebron, Hosp Santo Antonio Capuchos, Hosp Puerta Hierro, Univ Fed Rio Grande do Sul, Region Hosp Hovedstaden, Hannover Med Sch, German Liver Fdn, Univ Plymouth, Univ New S Wales, Cairo Univ, Orebro Univ Hosp, Univ Orebro, Ain Shams Univ, Dokuz Eylul Univ, Ctr Dis Anal CDA, Karolinska Inst, Exigo Consultores, Universidade Federal de São Paulo (UNIFESP), Hosp Carlos III, Univ Copenhagen, Direccao Geral Saude, Universidade Estadual de Campinas (UNICAMP), Wilhelminenspital Stadt Wien, Universidade de São Paulo (USP), Med Univ Vienna, Masaryk Univ, Univ Manitoba, Hlth Sci Ctr, European Liver Patients Assoc, Istanbul Univ, Univ British Columbia, Aalborg Univ Hosp, Katholieke Univ Leuven, Univ Western Ontario, Univ Dusseldorf, Univ Zurich Hosp, Univ Calgary, Univ Hosp, Natl Inst Publ Hlth, Univ Southhampton, Dalhousie Univ, Capital Dist Hlth Author, Assembleia Republ, Alfred Hosp, Monash Univ, UCL, Ctr Hosp Porto, JW Goethe Univ Hosp, Cantonal Hosp St Gallen, Egyptian Liver Res Inst & Hosp ELRIAH, Monash Hlth, Catholic Univ Louvain, Med Univ Graz, St Vincents Hosp, Univ Melbourne, Charles Univ Prague, Cent Mil Hosp, Deutsch Leberhilfe eV, Ghent Univ Hosp, Univ Ghent, Hasselt Univ, Med Univ Innsbruck, Natl Liver Inst, Copenhagen Univ Hosp, Univ Antwerp, Karolinska Univ Hosp, Bihl, Florian, Negro, Francesco, and Semela, David

Subjects
medicine.medical_specialty, diagnosis, prevalence, Prevalence, ddc:616.07, disease burden, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Virology, Epidemiology, medicine, 030212 general & internal medicine, Disease burden, Hepatitis, ddc:616, Hepatology, treatment, business.industry, Incidence (epidemiology), virus diseases, Hepatitis C, medicine.disease, mortality, 3. Good health, Infectious Diseases, Immunology, HCV, incidence, 030211 gastroenterology & hepatology, epidemiology, Human medicine, hepatitis C, business, Demography
Abstract

Gilead Sciences Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. for some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. the largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. the age distribution of cases differed between countries. in most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level. Arud Ctr Addict Med, CH-8005 Zurich, Switzerland Univ Leipzig, D-04109 Leipzig, Germany Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Fed Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Hosp Santa Maria, Ctr Hosp Lisboa Norte, Dept Gastroenterol, Lisbon, Portugal Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Ege Univ, Izmir, Turkey Ankara Univ, TR-06100 Ankara, Turkey Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Adv Tech Hlth Serv Res TAISS, Madrid, Spain Hosp Valle de Hebron, CIBERehd, Barcelona, Spain Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Region Hosp Hovedstaden, Region Hovedstaden, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany German Liver Fdn, Hannover, Germany Univ Plymouth, Peninsula Schools Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Cairo Univ, Cairo, Egypt Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Ctr Dis Anal CDA, Louisville, CO USA Karolinska Inst, Infect Dis Unit, Dept Med Huddinge, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Fac Ciencias Med, UNICAMP,Dept Clin Med, Grp Estudo Hepatites,Disciplina Doencas Infeccios, São Paulo, Brazil Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ São Paulo, Sch Med, São Paulo, Brazil Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ, Dept Med, Halifax, NS, Canada Dalhousie Univ, Dept Surg, Halifax, NS B3H 4H2, Canada Capital Dist Hlth Author, Serv Hepatol, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia UCL, UCL Inst Liver & Digest Hlth, Div Med, London, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal JW Goethe Univ Hosp, Frankfurt, Germany Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Egyptian Liver Res Inst & Hosp ELRIAH, Dakahliah, Egypt Monash Hlth, Melbourne, Vic, Australia Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Deutsch Leberhilfe eV, Cologne, Germany Ghent Univ Hosp, Ghent, Belgium Univ Ghent, B-9000 Ghent, Belgium Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium Med Univ Innsbruck, A-6020 Innsbruck, Austria Natl Liver Inst, Menoufia, Egypt Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Antwerp, B-2020 Antwerp, Belgium Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Web of Science

Published
2014

3. Common variant at 16p11.2 conferring risk of psychosis

Author

Steinberg, S., de Jong, S., Sigurdsson, E., Murray, R., Corvin, A., Gill, M., Morris, D., O'Neill, F. A., Kendler, K., Riley, B., 2, Wellcome Trust Case Control Consortium, Craddock, N., Owen, M. J., Vassos, E., O'Donovan, M. C., Thorsteinsdottir, U., Kong, A., Ehrenreich, H., Carracedo, A., Golimbet, V., Andreassen, O. A., Børglum, A. D., Mors, O., Mortensen, P. B., Giegling, I., Werge, T., Ophoff, R. A., Nöthen, M. M., Rietschel, M., Cichon, S., Ruggeri, M., Tosato, S., Palotie, A., St Clair, D., Rujescu, D., Breuer, R., Collier, D. A., Stefansson, H., Stefansson, K., Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Fraser, G., Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Walker, N., Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris C A, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Melle, I., Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Djurovic, S., Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Agartz, I., Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Tuulio-Henriksson, A., Mattheisen, M., Suvisaari, J., Lönnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., GROUP, Hougaard, D. M., Costas, J., Orntoft, T., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Abramova, L., Kaleda, V., Arrojo, M., Sanjuán, J., Arango, C., Etain, B., Demontis, D., Bellivier, F., Méary, A., Schürhoff, F., Szoke, A., Ribolsi, M., Magni, V., Siracusano, A., Sperling, S., Rossner, M., Christiansen, C., Jamain, S., Kiemeney, L. A., Franke, B., van den Berg, L. H., Veldink, J., Curran, S., Bolton, P., Poot, M., Staal, W., Rehnstrom, K., Kilpinen, H., Pietiläinen, O. P. H., Freitag, C. M., Meyer, J., Magnusson, P., Saemundsen, E., Martsenkovsky, I., Bikshaieva, I., Martsenkovska, I., Vashchenko, O., Raleva, M., Paketchieva, K., Lin, K., Stefanovski, B., Durmishi, N., Pejovic Milovancevic, M., Lecic Tosevski, D., Silagadze, T., Naneishvili, N., Mikeladze, N., Surguladze, S., Vincent, J. B., Farmer, A., Papiol, S., Mitchell, P. B., Wright, A., Schofield, P. R., Fullerton, J. M., Montgomery, G. W., Martin, N. G., Rubino, I. A., van Winkel, R., Kenis, G., De Hert, M., Huttenlocher, J., Réthelyi, J. M., Bitter, I., Terenius, L., Jönsson, E. G., Bakker, S., van Os, J., Jablensky, A., Leboyer, M., Bramon, E., Powell, J., deCODE Genet, IS-101 Reykjavik, Iceland Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA Univ Bonn, Inst Genom Math, Bonn, Germany Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany CHUS, Galician Fdn Genom Med SERGAS, Santiago De Compostela, Spain Aarhus Univ, Dept Biomed, Aarhus, Denmark Aarhus Univ, iSEQ, Ctr Integrat Sequencing, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark Fdn FondaMental, Creteil, France Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland Wellcome Trust Sanger Inst, Cambridge, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Neurosci, London, England Kings Coll London, London, England DFG Res Ctr Mol Physiol Brain CMPB, Gottingen, Germany Max Planck Inst Expt Med, Div Clin Neurosci, D-37075 Gottingen, Germany Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland Univ Iceland, Sch Med, Reykjavik, Iceland Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London, England Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80539 Munich, Germany Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany Univ Aberdeen, Dept Mental Hlth, Royal Cornhill Hosp, Aberdeen, Scotland Ravenscraig Hosp, Greenock, Scotland [Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict,Oslo Univ Hosp, Oslo, Norway Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland Univ Helsinki, Cent Hosp, Helsinki, Finland Natl Inst Hlth & Welf THL, Publ Hlth Genom Unit, Helsinki, Finland Univ Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark H Lundbeck & Co AS, Synapt Transmiss, Copenhagen, Denmark Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, Copenhagen, Denmark Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia CHUS, Serv Psychiat, Santiago De Compostela, Spain Univ Valencia, Network Ctr Biomed Res Mental Hlth CIBERSAM, Unit Psychiat, Fac Med, Valencia, Spain Univ Complutense, Hosp Gen Univ Gregorio Maranon, IiSGM, CIBERSAM, E-28040 Madrid, Spain Hop H Mondor A Chenevier, AP HP, Creteil, France Univ Paris Est, Fac Med, Creteil, France Univ Roma Tor Vergata, Dept Neurosci, Sect Psychiat, Rome, Italy Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany Nord Biosci, Herlev, Denmark Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England Radboud Univ Nijmegen, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany Univ Trier, Dept Neurobehav Genet, Trier, Germany Natl Univ Hosp Reykjavik, Dept Child & Adolescent Psychiat, Reykjavik, Iceland State Diagnost & Counseling Ctr, Kopavogur, Iceland Ukrainian Res Inst Social Forens Psychiat & Drug, Dept Child Adolescent Psychiat & Med Social Rehab, Kiev, Ukraine Univ Skopje, Dept Child & Adolescent Psychiat, Skopje, Macedonia Inst Mental Hlth, Belgrade, Serbia Univ Belgrade, Fac Med, Belgrade, Serbia Tbilisi State Med Univ TSMU, Dept Psychiat & Drug Addict, Tbilisi, Rep of Georgia Ilia State Univ, Social & Affect Neurosci Lab, Tbilisi, Rep of Georgia Ctr Addict & Mental Hlth CAMH, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada Prince Wales Hosp, Black Dog Inst, Randwick, NSW 2031, Australia Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia Neurosci Res Australia, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Queensland Inst Med Res, Brisbane, Qld 4006, Australia Catholic Univ Louvain, Univ Psychiat Ctr, Kortenberg, Belgium Maastricht Univ, European Grad Sch Neurosci EURON,Med Ctr, Sch Mental Hlth & Neurosci,Dept Psychiat & Psycho, South Limburg Mental Hlth Res & Teaching Network, Maastricht, Netherlands Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Hungary Karolinska Hosp & Inst, HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands Maastricht Univ, Dept Psychiat, Med Ctr, Maastricht, Netherlands Univ Western Australia, Graylands Hosp, CCRN, Perth, WA 6009, Australia UCL, Mental Hlth Sci Unit, London, England UCL, Inst Cognit Neurosci, London, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Psychosis Studies, London, England Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales Univ Santiago de Compostela, Biomed Network Res Ctr Rare Dis CIBERER, Galician Fdn Genom Med, Genom Med Grp, Santiago De Compostela, Spain Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark German Ctr Neurodegenerat Disorders DZNE, Bonn, Germany Univ Bonn, Inst Human Genet, Bonn, Germany Inst Neurosci & Med INM 1, Julich, Germany Univ Verona, Sect Psychiat, I-37100 Verona, Italy Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA Univ Helsinki, Dept Med Genet, Helsinki, Finland Univ Cent Hosp, Helsinki, Finland Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany Eli Lilly & Co Ltd, Erl Wood Manor, Windlesham, Surrey, England, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and RS: MHeNs - R2 - Mental Health

Subjects
Oncology, Male, association, Bipolar disorder, cross-disorder, schizophrenia, 1p11.2, Bipolar Disorder, International Cooperation, Genome-wide association study, Disease, 0302 clinical medicine, Risk Factors, Epidemiology, Odds Ratio, Medicine, genetics [Schizophrenia], Oligonucleotide Array Sequence Analysis, Genetics, Aged, 80 and over, bipolar disorder, 0303 health sciences, Middle Aged, 16p11.2, 3. Good health, Europe, Psychiatry and Mental health, genetics [Chromosomes, Human, Pair 16], epidemiology [Bipolar Disorder], Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], genetics [Polymorphism, Single Nucleotide], Female, Adult, medicine.medical_specialty, Psychosis, Genotype, complications [Bipolar Disorder], epidemiology [Schizophrenia], Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, complications [Schizophrenia], Internal medicine, mental disorders, Humans, Genetic Predisposition to Disease, ddc:610, Molecular Biology, Settore MED/25 - Psichiatria, 030304 developmental biology, Aged, Chromosome Aberrations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Gene Expression Profiling, Odds ratio, medicine.disease, Schizophrenia, Autism, business, Body mass index, genetics [Bipolar Disorder], 030217 neurology & neurosurgery, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders). National Institute of Mental Health N01 MH900001 MH074027 1U24MH081810 R01 MH078075 Eli Lilly and Company Pritzker Neuropsychiatric Disorders Research Fund L.L.C. Massachusetts General Hospital in Boston, MA (NIMH) 2N01MH080001-001 Wellcome Trust 076113 085475 075491/Z/04 085475/B/08/Z 085475/Z/08/Z Medical Research Council G0601030 Anthony P Monaco, PI, University of Oxford National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) 01GS08144 01GS08147 Centre of Excellence for Complex Disease Genetics of the Academy of Finland 213506 129680 Biocentrum Helsinki Foundation Research Program for Molecular Medicine, Faculty of Medicine, University of Helsinki Stanley Medical Research Institute Danish Council for Strategic Research 2101-07-0059 H Lundbeck A/S; the Research Council of Norway 163070/V50 Danish Medical Research Council South-East Norway Health Authority 2004-123 Medical Research Council Ministerio de Sanidad y Consumo, Spain PI081522 Xunta de Galicia 08CSA005208PR Swedish Research Council Wellcome Trust Case Control Consortium 2 Max Planck Society; Saarland University T6 03 10 00-45 Netherlands Foundation for Brain Research (Hersenstichting) 2008(1).34 2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 HEALTH-F4-2009-242257 info:eu-repo/grantAgreement/EC/FP7/218251

Published
2014

4. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations

Author

Rosana Shuhama, Gonzalo López, Viviana Storbini, Tolga Binbay, Ma Soledad Olmeda, Maria Calem, Marina Mihaljevic, Christos Pantelis, Halis Ulaş, Eva Velthorst, Jeroen Decoster, J. Malte Bumb, Ruud van Winkel, E. Cem Atbasoglu, Wolfgang Viechtbauer, Mirella Ruggeri, Erich Studerus, Daniele La Barbera, Domenico Berardi, Anita Riecher-Rössler, Stefan Borgwardt, Elsje van der Ven, Charlotte Rapp, Desiree Hilboll, Mark van der Gaag, Chiara Bonetto, Marie-Odile Krebs, Silvia Tenan, Monika Schlögelhofer, Robin M. Murray, Caterina La Cascia, Philip McGuire, Simona A. Stilo, Desmond Campbell, Fabienne Harrisberger, Teresa Sánchez, Catherine Derom, Franck Schürhoff, Philippe Delespaul, Jose Luis Santos, Emilio Sánchez, Stephan Ruhrmann, Luigi Rocco Chiri, Sabrina Cruz, Handan Noyan, Dominika Julkowski, Celso Arango, Merete Nordentoft, Stacey S. Cherny, Anne-Marie Galliot, Daniella van Dam, María Pouso, Asier Urruela Mora, G. Paul Amminger, Enrique García Bernardo, Ahmet Ayer, Tijana Mirjanic, Andrei Szöke, Anna Walter, Antonio Lasalvia, Isla Humphreys, Flora Frijda, Lieuwe de Haan, Neus Barrantes-Vidal, Nigel Williams, Burçin Cihan, Matthew J. Kempton, Ceren Akdeniz, Tamar Kraan, Andrea Tortelli, Barnaby Nelson, Marta Di Forti, Angelo Fioritti, Pedro Cuadrado, Eylem Sahin Cankurtaran, Emanuel Schwarz, Andreas Meyer-Lindenberg, Ilaria Tarricone, Laura Ferraro, Dan Rujescu, Anne-Marie Tronche, Laura Roldan, Bibiana Cabrera, Alp Üçok, Craig Morgan, Julio Sanjuán, Mauro Braca, Julio Bobes, Eric Y.H. Chen, Michael Conlon O'Donovan, Peter Holmans, Harald N. Aschauer, Sarah Ittig, Covadonga Martínez, Iris Lasser, Emiliano González, Aitziber Emaldi Cirión, Rachele Sartorio, F. Seminerio, Rodrigo A. Bressan, Ulrich Reininghaus, Elisa Brietzke, François Bourque, G Tripoli, Inez Myin-Germeys, Aziz Ferchiou, Gemma Modinos, Grégoire Baudin, Fabienne Soguel-Dit-Piquard, Cristina Marta Del-Ben, Gabriele Sachs, Elçin Akturan, Manuel Arrojo, Thomas R. Kwapil, Alice Mulè, Eva Mª Díaz Mesa, Federico Chierzi, Köksal Alptekin, Floor J. van der Meer, Pak C. Sham, Jim van Os, Adanna Onyejiaka, Mara Parellada, Bart P. F. Rutten, Jeanne Vilain, Michael John Owen, Sarah Tosato, Haldan Soygür, A.M. Marinaro, Stefania Tognin, Evert Thiery, Cathrin Rohleder, Mary Cannon, Miaoxin Li, F. Markus Leweke, Marc De Hert, Marta Rapado, Maria Gabriella Minenna, Pierre-Michel Llorca, Alexander Richards, Stéphane Jamain, Elles Messchaert, Nadja P. Maric, Semra Ulusoy, Elisa Ira, Peter G. Jones, Paulo Rossi Menezes, Patrick D. McGorry, Bernadette Winklbaur, Stephanie Beards, Nadine Burger, Güvem Gümüş-Akay, Marion Leboyer, James B. Kirkbride, Sinan Guloksuz, Ary Gadelha, E. Bulzacka, Carlos M. Romeo-Casabona, Gülşah Karadayı, Jean-Paul Selten, José Juan Rodríguez Solano, Kathryn Hubbard, Estela Jiménez, Thomas Charpeaud, Nikos C. Stefanis, Lucia Sideli, Miguel Bernardo, Jean-Romain Richard, Ivonne Donegani, Marco Seri, Lucia Valmaggia, Julia Paruch, Catherine van Zelst, Meram Can Saka, Heike Tost, Renata Smieskova, Thomas Marcacci, Nicholas John Craddock, Berna Binnur Akdede, Joachim Klosterkötter, Richard Bruggeman, Charlotte Gayer-Anderson, Sanja Andric, Elena Bonora, Angel Carracedo, Hasan Karadağ, Paula Cristobal, ANS - Amsterdam Neuroscience, Adult Psychiatry, Graduate School, Perceptual and Cognitive Neuroscience (PCN), Maastricht Univ, Kings Coll London, Mondriaan Mental Hlth Trust, Univ Groningen, Cardiff Univ, Cent Inst Mental Hlth, Dokuz Eylul Univ, Istanbul Univ, Ankara Univ, Yale Univ, Middle E Tech Univ, Diskapi YB Res & Training Hosp, Turkish Federat Schizophrenia Assoc, Ataturk Training & Res Hosp, Manisa Mental Hlth Hosp, Univ Complutense, Univ Barcelona, Univ Valencia, Univ Oviedo, Univ Santiago de Compostela, Hosp Virgen de la Luz, Hosp Univ Infanta Leonor Hosp Virgen Torre, Hosp Clin Univ, Hosp Psiquiatr Conxo, Univ Amsterdam, Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Parnassia Psychiat Inst, Rivierduinen Psychiat Inst, Grp Hosp Mondor, Hop Henri Mondor, Univ Paris Est, Fdn Fondamental, CMP B CHU, Univ Auvergne, EPS Maison Blanche, UPC KU Leuven, UPC, Katholieke Univ Leuven, Assoc Sci Res Multiple Births, Univ Ghent, Univ Athens, Med Univ Vienna, Psychiat Univ Clin Basel, Univ Cologne, Univ Hong Kong, Univ Basque Country, Univ Zaragoza, Univ Cambridge, UCL, Royal Coll Surgeons Ireland, Univ Munich, Univ Bologna, Local Hlth Trust, Univ Palermo, P Giaccone Gen Hosp, Univ Melbourne, Universidade de São Paulo (USP), Univ Verona, Copenhagen Univ Hosp, Univ Paris 05, Univ Autonoma Barcelona, St Pere Claver Fundacio Sanitaria, Univ N Carolina, CIBERSAM, Universidade Federal de São Paulo (UNIFESP), Univ Belgrade, van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, Mirjanic T, Clinical Psychology, EMGO+ - Mental Health, Van Os, J., Rutten, B., Myin Germeys, I., Delespaul, P., Viechtbauer, W., Van Zelst, C., Bruggeman, R., Reininghaus, U., Morgan, C., Murray, R., Di Forti, M., Mcguire, P., Valmaggia, L., Kempton, M., Gayer Anderson, C., Hubbard, K., Beards, S., Stilo, S., Onyejiaka, A., Bourque, F., Modinos, G., Tognin, S., Calem, M., O'Donovan, M., Owen, M., Holmans, P., Williams, N., Craddock, N., Richards, A., Humphreys, I., Meyer Lindenberg, A., Leweke, F., Tost, H., Akdeniz, C., Rohleder, C., Bumb, J., Schwarz, E., Alptekin, K., Üçok, A., Saka, M., Atbagoǧlu, E., Gülöksüz, S., Gumus Akay, G., Cihan, B., Karadaǧ, H., Soygür, H., Cankurtaran, E., Ulusoy, S., Akdede, B., Binbay, T., Ayer, A., Noyan, H., Karadayi, G., Akturan, E., Ulaş, H., Arango, C., Parellada, M., Bernardo, M., Sanjuán, J., Bobes, J., Arrojo, M., Santos, J., Cuadrado, P., Solano, J., Carracedo, A., Bernardo, E., Roldán, L., López, G., Cabrera, B., Cruz, S., Mesa, E., Pouso, M., Jiménez, E., Sánchez, T., Rapado, M., González, E., Martínez, C., Sánchez, E., Olmeda, M., De Haan, L., Velthorst, E., Van Der Gaag, M., Selten, J., Van Dam, D., Van Der Ven, E., Van Der Meer, F., Messchaert, E., Kraan, T., Burger, N., Leboyer, M., Szoke, A., Schürhoff, F., Llorca, P., Jamain, S., Tortelli, A., Frijda, F., Vilain, J., Galliot, A., Baudin, G., Ferchiou, A., Richard, J., Bulzacka, E., Charpeaud, T., Tronche, A., De Hert, M., Van Winkel, R., Decoster, J., Derom, C., Thiery, E., Stefanis, N., Sachs, G., Aschauer, H., Lasser, I., Winklbaur, B., Schlögelhofer, M., Riecher Rössler, A., Borgwardt, S., Walter, A., Harrisberger, F., Smieskova, R., Rapp, C., Ittig, S., Soguel Dit Piquard, F., Studerus, E., Klosterkötter, J., Ruhrmann, S., Paruch, J., Julkowski, D., Hilboll, D., Sham, P., Cherny, S., Chen, E., Campbell, D., Li, M., Romeo Casabona, C., Cirión, A., Mora, A., Jones, P., Kirkbride, J., Cannon, M., Rujescu, D., Tarricone, I., Berardi, D., Bonora, E., Seri, M., Marcacci, T., Chiri, L., Chierzi, F., Storbini, V., Braca, M., Minenna, M., Donegani, I., Fioritti, A., LA BARBERA, D., LA CASCIA, C., Mulè, A., Sideli, L., Sartorio, C., Ferraro, L., Tripoli, G., Seminerio, F., Marinaro, A., Mcgorry, P., Nelson, B., Amminger, G., Pantelis, C., Menezes, P., Del Ben, C., Tenan, S., Shuhama, R., Ruggeri, M., Tosato, S., Lasalvia, A., Bonetto, C., Ira, E., Nordentoft, M., Krebs, M., Barrantes Vidal, N., Cristóbal, P., Kwapil, T., Brietzke, E., Bressan, R., Gadelha, A., Maric, N., Andric, S., Mihaljevic, M., Mirjanic, T., Psychiatrie & Neuropsychologie, Promovendi MHN, and RS: MHeNs - R2 - Mental Health

Subjects
URBANICITY, Schizophrenia (object-oriented programming), CHILDHOOD, Genome-wide association study, VARIANTS, Social Environment, psychosi, 03 medical and health sciences, 0302 clinical medicine, PSYCHOSIS, epidemiology, gene-environment interaction, genetics, psychosis, schizophrenia, SDG 3 - Good Health and Well-being, RISK-FACTOR, Settore M-PSI/08 - Psicologia Clinica, Genetic variation, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Gene, Settore MED/25 - Psichiatria, METAANALYSIS, Scale (chemistry), Psychosis, Genetic variants, Environment and Schizophrenia Invited, CANNABIS USE, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Evolutionary biology, Identification (biology), Schizophrenic Psychology, Population Risk, genetic, Psychology, FOLLOW-UP, 030217 neurology & neurosurgery, FUTURE-DIRECTIONS, Clinical psychology
Abstract

European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. Maastricht Univ, Med Ctr, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci,South Limburg Mental H, NL-6200 MD Maastricht, Netherlands Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England Mondriaan Mental Hlth Trust, Maastricht, Heerlen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Rob Giel Clin Res, Univ Ctr Psychiat, Groningen, Netherlands Kings Coll London, Inst Psychiat, Dept Hlth Serv & Populat Res, London WC2R 2LS, England Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England Cardiff Univ, MRC, Ctr Neuropsychiat Genet, Cardiff CF10 3AX, S Glam, Wales Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany Dokuz Eylul Univ, Sch Med, Dept Psychiat, Konak, Turkey Istanbul Univ, Istanbul Fac Med, Dept Psychiat, Psychot Disorders Res Unit, Istanbul, Turkey Ankara Univ, Sch Med, Dept Psychiat, Cebeci Hosp, TR-06100 Ankara, Turkey Ankara Univ, Brain Res Ctr, TR-06100 Ankara, Turkey Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA Middle E Tech Univ, Dept Psychol, TR-06531 Ankara, Turkey Diskapi YB Res & Training Hosp, Ankara, Turkey Turkish Federat Schizophrenia Assoc, Ankara, Turkey Ataturk Training & Res Hosp, Psychiat Clin, Ankara, Turkey Manisa Mental Hlth Hosp, Manisa, Turkey Istanbul Univ, Expt Med Res Inst, Dept Adv Neurol Sci, Istanbul Fac Med, Istanbul, Turkey Univ Complutense, IiSGM CIBERSAM, Dept Child & Adolescent Psychiat, Hosp Gen Univ Gregorio Maranon,Sch Med, E-28040 Madrid, Spain Univ Barcelona, Dept Psychiat, Hosp Clin, IDIBAPS,Ctr Invest Biomed Red Salud Mental CIBERS, Barcelona, Spain Univ Valencia, Sch Med, Dept Psychiat, Ctr Invest Biomed Red Salud Mental CIBERSAM, Valencia, Spain Univ Oviedo, Sch Med, Dept Med,Psychiat Area, Ctr Invest Biomed Red Salud Mental CIBERSAM, Oviedo, Spain Univ Santiago de Compostela, Dept Mental Hlth & Drug Addit Assistance, Hlth Serv Galicia,Psychiat Genet Grp IDIS, Hosp Clin,Ctr Invest Biomedica Red Salud Mental C, Santiago de Compostela 15706, Spain Hosp Virgen de la Luz, Serv Psiquiat, Dept Psychiat, Cuenca, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Villa de Vallecas Mental Hlth Ctr, Villa de Vallecas Mental Hlth Dept, Madrid, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Puente de Vallecas Mental Hlth Dept, Ctr Salud Mental Puente Vallecas, Madrid, Spain Hosp Clin Univ, Fdn Publ Galega Med Xenomica, Santiago de Compostela, Spain Univ Complutense, Sch Med, Hosp Gen Univ Gregorio Maranon, Dept Psychiat, E-28040 Madrid, Spain Hosp Psiquiatr Conxo, Santiago de Compostela, Spain Univ Amsterdam, Acad Med Ctr, Early Psychosis Sect, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands EMGO Inst Hlth & Care Res, Amsterdam, Netherlands Parnassia Psychiat Inst, Dept Psychosis Res, the Hague, Netherlands Rivierduinen Psychiat Inst, Leiden, Netherlands Grp Hosp Mondor, AP HP, Creteil, France Hop Henri Mondor, INSERM, U955, Equipe 15, F-94010 Creteil, France Univ Paris Est, Fac Med, Creteil, France Fdn Fondamental, Creteil, France CMP B CHU, F-63003 Clermont Ferrand 1, France Univ Auvergne, EA 7280, Clermont Ferrand, France EPS Maison Blanche, Paris, France UPC KU Leuven, Dept Neurosci, UPC, Kortenberg, Belgium UPC, Dept Neurosci, Res Grp Psychiat, Leuven, Belgium Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Human Genet, Leuven, Belgium Assoc Sci Res Multiple Births, Ghent, Belgium Univ Ghent, Dept Neurol, Ghent Univ Hosp, B-9000 Ghent, Belgium Univ Athens, Sch Med, Eginit Hosp, Athens 11528, Greece Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria Psychiat Univ Clin Basel, Ctr Gender Res & Early Detect, Basel, Switzerland Psychiat Univ Clin Basel, Diagnost & Crisis Intervent Ctr, Basel, Switzerland Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome Prov Govt Bisk, Bilbao, Bizkaia, Spain Univ Zaragoza, Zaragoza, Spain Univ Cambridge, Dept Psychiat, Cambridge, England UCL, Div Psychiat, London, England Royal Coll Surgeons Ireland, Beaumont Hosp, Educ & Res Ctr, Dept Psychiat, Dublin 9, Ireland Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, Munich, Germany Univ Bologna, Alma Mater Studiorium, Psychiat Unit, Dept Med & Surg Sci, Bologna, Italy Univ Bologna, Alma Mater Studiorium, Genet Unit, Dept Med & Surg Sci, Bologna, Italy Local Hlth Trust, Dept Mental Hlth & Pathol Addict, Bologna, Italy Univ Palermo, Sect Psychiat, Dept Expt Biomed & Clin Neurosci, Palermo, Italy P Giaccone Gen Hosp, Unit Psychiat, Palermo, Italy Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia Univ Melbourne, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia Univ São Paulo, Fac Med, Dept Med Prevent, BR-01246903 São Paulo, Brazil Univ São Paulo, Nucleo Pesquina Saude Mental Populac, São Paulo, Brazil Univ São Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, Brazil Univ Verona, Sect Psychiat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy Copenhagen Univ Hosp, Res Unit, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark Univ Paris 05, Fac Med, Serv Hosp Univ, Hop St Anne, Paris, France Univ Autonoma Barcelona, Dept Psicol Clin & Salut, E-08193 Barcelona, Spain St Pere Claver Fundacio Sanitaria, Dept Salut Mental, Barcelona, Spain Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA CIBERSAM, Spanish Mental Hlth Res Network, Barcelona, Spain Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil Univ Belgrade, Sch Med, Beograd, Serbia Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil European Community: HEALTH-F2-2009-241909 Web of Science

Published
2014

5. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm

Author

Altaf Alam, K. Saeed, N. Nugrahini, Fadi H. Mourad, Andri Sanityoso Sulaiman, Abdul Rahman Bizri, Jon G. Jonasson, Liana Gheorghe, S. Alawadhi, Ala I. Sharara, Sarah Blach, Rino Alvani Gani, Do Young Kim, M. Alzaabi, Young Seok Kim, Matti Maimets, S. Priohutomo, A. Löve, Saeed Hamid, Abdullah M. Assiri, H. Al Quraishi, Adel Alqutub, G. Tayyab, Junko Tanaka, H. Qureshi, A. Salamat, P. Aldins, M. S. Choi, M. T. Barakat, Reza Malekzadeh, M. Sadik, Kwang Hyub Han, Young-Suk Lim, J. Videčnik-Zorman, A. Abdou, Jacques E Mokhbat, Zaigham Abbas, Khalid Alswat, G. Sigmundsdottir, B. Karlsdottir, Marwa Sultan, K. Al Jaberi, Devin Razavi-Shearer, A. Al Rifai, Chris Estes, Abdullah S. Alghamdi, A. Sanityoso Sulaiman, Béla Hunyady, F. Al Braiki, B. Sigurdardottir, Ieva Tolmane, Kathryn Razavi-Shearer, S. El Khoury, Gabor Horvath, Y. Al Serkal, M. Taha, Hamad I. Al-Ashgar, Cesar Yaghi, Abdulrahman Aljumah, Danute Speiciene, Riina Salupere, Irsan Hasan, S. Fakhry, Homie Razavi, Evy Yunihastuti, F. Al Hosani, M. A. Al Mulla, Faisal M. Sanai, Mohamed A. Babatin, N. Andrea, L. Al-Dabal, S. Gregorcic, Arif Nawaz, R. Al-Hakeem, E. S. El Hassan, R. Husni, M. Siddiq, David H. Muljono, Adrian Goldis, A. Almessabi, Jonathan Schmelzer, Mojca Maticic, Laurentius A. Lesmana, A. Baqir, Ibrahim Altraif, Faisal Abaalkhail, Shahin Merat, Mihály Makara, A. Abourached, Jonas Valantinas, Asad Chaudhry, T. Diab, M. Ud Din, Muhammad S. Memon, Jessie Gunter, R. A. Sayegh, Seyed Moayed Alavian, A. M. Siddiqui, H. Fridjonsdottir, Bader Faiyaz Zuberi, M. Umar, Magnus Gottfredsson, Baiba Rozentale, Agita Jeruma, Samsuridjal Djauzi, Almoutaz Hashim, A. Ghafoor Khan, Ottar M. Bergmann, Z. Koutoubi, M. A. Yusuf, H. Tarifi, A. Sibley, Faleh Z. Al-Faleh, Wasim Jafri, P. Rassam, J. I. Farooqi, S. Olafsson, Behzad Hajarizadeh, Valentina Liakina, M. Al Khatry, Ctr Dis Anal, Natl Liver Inst, JW Goethe Univ Hosp, Univ Calgary, Ankara Univ, Hosp Santo Antonio Capuchos, Med Univ Innsbruck, Universidade de São Paulo (USP), Hop Henri Mondor, Adv Tech Hlth Serv Res TAISS, Ege Univ, Karolinska Inst, Karolinska Univ Hosp, Univ Leipzig, Osped Cantonale, Univ Montreal, Fed Univ State Rio de Janeiro, Arud Ctr Addict Med, Hosp Valle de Hebron, Hosp Puerta Hierro, Univ Fed Rio Grande do Sul, Odense Univ Hosp, Reg Hosp Hovedstaden, Universidade Federal do Rio de Janeiro (UFRJ), Univ Plymouth, Univ New S Wales, Cairo Univ, Orebro Univ Hosp, Univ Orebro, Ain Shams Univ, Dokuz Eylul Univ, Exigo Consultores, Universidade Federal de São Paulo (UNIFESP), Inst Clin & Expt Med, Hosp Carlos III, Univ Copenhagen, Direccao Geral Saude, Universidade Estadual de Campinas (UNICAMP), Wilhelminenspital Stadt Wien, Med Univ Vienna, Masaryk Univ, Univ Manitoba, Hlth Sci Ctr, European Liver Patients Assoc, Istanbul Univ, Univ British Columbia, Aalborg Univ Hosp, Katholieke Univ Leuven, Hosp Santa Maria, Univ Western Ontario, Univ Dusseldorf, Univ Libre Brussels, Univ Hosp, Natl Inst Publ Hlth, Univ Southhampton, Dalhousie Univ & Hepatol Serv, Assembleia Republ, Alfred Hosp, Monash Univ, UCL, Nottingham Univ Hosp NHS Trust, Biomed Res Unit, Ctr Hosp Porto, Cantonal Hosp St Gallen, Univ Toronto, Egyptian Liver Res Inst & Hosp, Monash Hlth, Catholic Univ Louvain, Med Univ Graz, St Vincents Hosp, Univ Melbourne, Charles Univ Prague, Cent Mil Hosp, Univ Antwerp, Deutsch Leberhilfe eV, Ghent Univ Hosp, Univ Ghent, Hannover Med Sch, Copenhagen Univ Hosp, Univ Zurich Hosp, Bihl, Florian, Negro, Francesco, and Semela, David

Subjects
Pediatrics, medicine.medical_specialty, diagnosis, Cost effectiveness, Hepatitis C virus, prevalence, ddc:616.07, medicine.disease_cause, disease burden, Liver disease, Virology, Epidemiology, medicine, Disease burden, ddc:616, treatment, Hepatology, business.industry, Incidence (epidemiology), Hepatitis C, medicine.disease, mortality, Infectious Diseases, HCV, Immunology, incidence, epidemiology, Human medicine, hepatitis C, Viral hepatitis, business
Abstract

Gilead Sciences The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. in addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing. Ctr Dis Anal, Louisville, CO 80027 USA Natl Liver Inst, Menoufia, Egypt JW Goethe Univ Hosp, Frankfurt, Germany Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada Ankara Univ, Dept Gastroenterol, Sch Med, TR-06100 Ankara, Turkey Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal Med Univ Innsbruck, A-6020 Innsbruck, Austria Univ São Paulo, Sch Med, São Paulo, Brazil Hop Henri Mondor, Serv Hepatogastroenterol, F-94010 Creteil, France Adv Tech Hlth Serv Res TAISS, Madrid, Spain Ege Univ, Izmir, Turkey Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden Ankara Univ, TR-06100 Ankara, Turkey Univ Leipzig, D-04109 Leipzig, Germany Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland Univ Montreal, Dept Med, Liver Unit, Montreal, PQ H3C 3J7, Canada Fed Univ State Rio de Janeiro, Dept Gastroenterol, Rio de Janeiro, Brazil Arud Ctr Addict Med, Zurich, Switzerland Hosp Valle de Hebron, CIBERehd, Barcelona, Spain Hosp Puerta Hierro, Madrid, Spain Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark Reg Hosp Hovedstaden, Copenhagen, Denmark Univ Fed Rio de Janeiro, Dept Clin Med, Rio de Janeiro, Brazil Univ Plymouth, Peninsula Sch Med & Dent, Plymouth PL4 8AA, Devon, England Univ New S Wales, Kirby Inst, Sydney, NSW, Australia Cairo Univ, Cairo, Egypt Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden Ain Shams Univ, Cairo, Egypt Dokuz Eylul Univ, Izmir, Turkey Karolinska Inst, Karolinska Univ Hosp, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden Exigo Consultores, Alhos Vedros, Portugal Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic Hosp Carlos III, CIBERehd, Madrid, Spain Univ Copenhagen, Copenhagen, Denmark Direccao Geral Saude, Lisbon, Portugal Univ Estadual Campinas, Disciplina Doencas Infecciosas, Dept Clin Med, Grp Estudo Hepatites,Fac Ciencias Med,UNICAMP, São Paulo, Brazil Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria Univ São Paulo, Sch Med, Div Gastroenterol & Hepatol, São Paulo, Brazil Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada European Liver Patients Assoc, St Truiden, Belgium Istanbul Univ, Istanbul, Turkey Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, BC V5Z 1M9, Canada Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium Hosp Santa Maria, Dept Gastroenterol, Ctr Hosp Lisboa Norte, Lisbon, Portugal Univ Western Ontario, Div Gastroenterol, London, ON, Canada Univ Dusseldorf, Dusseldorf, Germany Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland Univ Hosp, Div Clin Pathol, Geneva, Switzerland Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic Univ Southhampton, Southampton, England Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Med, Halifax, NS, Canada Dalhousie Univ & Hepatol Serv, Capital Dist Hlth Author, Queen Elizabeth II Hlth Sci Ctr, Dept Surg, Halifax, NS, Canada Univ British Columbia, Dept Gastroenterol, Vancouver, BC V5Z 1M9, Canada Assembleia Republ, Lisbon, Portugal Alfred Hosp, Melbourne, Vic, Australia Monash Univ, Melbourne, Vic 3004, Australia UCL, Div Med, UCL Inst Liver & Digest Hlth, London, England Hop Henri Mondor, Dept Sante Publ, F-94010 Creteil, France Nottingham Univ Hosp NHS Trust, Nottingham, England Biomed Res Unit, Nottingham, England Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 1L7, Canada Egyptian Liver Res Inst & Hosp, Dakahliah, Egypt Monash Hlth, Melbourne, Vic, Australia Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium Med Univ Graz, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia Univ Melbourne, Melbourne, Vic, Australia Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic Cent Mil Hosp, Prague, Czech Republic Univ Antwerp, B-2020 Antwerp, Belgium Deutsch Leberhilfe eV, Cologne, Germany Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Belgium Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany Copenhagen Univ Hosp, Hvidovre, Denmark Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, Brazil Universidade Federal de São Paulo, Div Infect Dis, São Paulo, Brazil Web of Science

Published
2014

6. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial.

Author

Guilhot F, Rigal-Huguet F, Guilhot J, Guerci-Bresler AP, Maloisel F, Rea D, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Jourdan E, Berger M, Fouillard L, Alexis M, Legros L, Rousselot P, Delmer A, Lenain P, Escoffre Barbe M, Gyan E, Bulabois CE, Dubruille V, Joly B, Pollet B, Cony-Makhoul P, Johnson-Ansah H, Mercier M, Caillot D, Charbonnier A, Kiladjian JJ, Chapiro J, Penot A, Dorvaux V, Vaida I, Santagostino A, Roy L, Zerazhi H, Deconinck E, Maisonneuve H, Plantier I, Lebon D, Arkam Y, Cambier N, Ghomari K, Miclea JM, Glaisner S, Cayuela JM, Chomel JC, Muller M, Lhermitte L, Delord M, Preudhomme C, Etienne G, Mahon FX, and Nicolini FE

Subjects
Adult, Aged, Aged, 80 and over, Cytarabine administration & dosage, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Imatinib Mesylate administration & dosage, Interferon-alpha administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Polyethylene Glycols administration & dosage, Prognosis, Prospective Studies, Recombinant Proteins administration & dosage, Survival Rate, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Abstract

The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Published
2021
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