HDV - ANRS
Transcription
HDV - ANRS
Hepatite Delta, o desafio amazônico Christian Trepo Hepato-Gastro-Enterologia – Hospital de la CroixRousse, Lyon –– França INSERM Unit Research U1052 – Lyon – França HEPATITIS VIRUSES DISCOVERY HBV Blumberg et al 1963 Serology HDV HAV Feinstone et al Rizzetto et al 1973 1977 IEM (stool) Serology, IF (liver) HEV Balayan et al 1983 Serology, IEM (stool) HCV Houghton et al 1989 Cloning (liver) Cirrhosis Evolution of Hepatitis D Compared to Hepatitis B and C HDV Fibrosis HBV HCV 0 Years 1980s: Global Anti-HDV Prevalence in HBsAg Carriers (15,000,000 Positive) Hepatitis B in Brazil HBs Ag prevalence GuyanaFrancaise Roraima high Acre HIGHEST Amazonas Hepatitis in Amazonia Serra do Navio Tocantins Carajás Pará Moderate Fortaleza No data Rondônia Mato D. Moderate Grosso F. Major cause of Fulminant Bahia Bahia Goiás Pernambu co Aracaju Moderate Minas Low Gerais Espírito Santo São Paulo do Sul Rio de Janeiro Paraná Mato Grosso Fonseca, 1993 Arraes et al., 2001 Santa Catarina (West) R. G. Sul Lowest Endemicity High - > 8% Moderate - 1,0 -3,0% Low - < 1,0% HBV - Genotype distribution in Brazil and South America F > Native population / Amerindians A> Non-Native populations/Caucasians and African decendents D> Related to Italian immigration B/C in a few areas of Asian immigration F C A B D/E C D B D AG D B DC B G A/F Aa A,B,CD C A D A,B,C,D,F Norder et al. 1994; Arauz-Ruiz et al. 1997; Sitnik et al. 1999; Swenson PD. Et al. 2001;Moriya T. et al. 2002 Viana et al , 2003 Variabilité génétique du VHD D'après Radjef et al 2004 8 génotypes Distribution géographique Prévalence des génotypes de VHB et de VHD au Brésil A1, D3 HDV-1 F>A F>A HDV-3 HDV-3 A1>F D>A2 A1>D3>F2 au Brésil F2>A1>D3 en Amazonie A1, D Adapté: Roncato, 2008; Souto, 2008 A1 ANRS-BRAZIL HEPATITIS CLINICAL RESEARCH 1) Repriorisation of hepatitis - 2) Brazil and France are pioneers : long standing fruitful collaboration for 20 years : - 3) WHO resolution … and Road map 40 international publication and 15 Brazilian HBV, HCV and HDV all culminate in Amazonia active programmes are ongoing - LIA/ANRS project 4) Results of studies are most promising and breakthroughs are at hand. Objectives 1) 2) Describe genomic variations of HBV/HDV among hepatitis cases in Salvador (BA), Cruzeiro do Sul (AC), Rio Branco (AC) Porto Velho (RO) Correlate it with disease severity Population de l´étude Zone géographique Taille de l´échantillon estimée: 3320 patients 3000 patients VHB+ 300 pacients VHD+ 20 patients Fièvre Noire Labrea Argentina et Foz do Iguaçu • Fréquences génotypiques des VHB et VHD de 92 patients. • VHD génotype 3 Mutant Hybridation des produits de PCR nichée du VHD avec la sonde de génotype 3 Séquences du VHD génotype 3 sauvage et mutant F193Y • L'état clinique et sérologique associée à l'âge, le sexe et le VHB / VHD génotypes des patients co-infectés. 17 patients HDV 3 mut/HBV non-F 75.5% (12/17) hépatite chronique 23.5% (4/17) cirrhose (2= 2.833; p=0.092) CONCLUSION (2) : PATHOGENIC CORRELATIONS 1) Most severe cases including fast progressive and fulminant hepatitis associated with coinfection HBV/F and HDV/3 2) Non F genotype in Amazonia are often associated with mutant genotype 3 3) Strong correlation between mutant genotype 3 and less severe liver disease HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV Genotype 3 carriers Alan Kay1, Edinete Melo da Silva1, Hermes Pedreira2, Suiane Negreiros3, Cirley Lobato3, Wornei Braga4, Richard Muwonge6, Paul Dény1, Mitermayer Reis2, Fabien Zoulim1,5, Christian Trepo1,5, Argemiro d´Oliveira Jr7, Juan Miguel Salcedo7, Maria Isabel Schinoni7 and Raymundo Parana2,7 1INSERM, U1052, Lyon, France; 2Laboratory of Pathology and Molecular Biology, CPqGM/FIOCRUZ, Salvador, Brazil; 3Acre State Secretariat of Health, Rio Branco, Brazil; 4Institute of Tropical Medicine of Amazonas, Manaus, Brazil; 5Service d'HépatoGastroentérology, Hôpital de la Croix-Rousse, Lyon, France; 6International Agency for Research on Cancer (IARC) /World Health Organization (WHO), Lyon, France; 7University Hospital, Federal University of Bahia, Amazon Hepatitis Group, Salvador, Brazil. Journal of Viral Hepatitis, Soumis le 25 octobre 2013 PERSPECTIVES (1) : 2 MERIEUX FOUNDATION PROJECTS 1) 2014 : Establish Charles Mérieux Training Center in Salvador to teach health professionals from Amazon regions 2) 2014-15 : Build Rodolphe Mérieux Laboratory for molecular virology diagnostics in Rio Branco University Hospital In Salvador: 1.Creation of a well-designed laboratory for molecular diagnostics at the university hospital (HUPES) of Salvador/Bahia 2.Development and standardizing of qualitative and quantitative molecular diagnostics for HBV, HCV and HDV 3.Basic and advanced teaching of laboratory technicians of Salvador and Acre 4.Monitoring and supervising of the activities of the local labs in the North of Brazil 5.Coordination with Amazon Centers In Acre: 1.Evaluation and analysis of the actual situation of molecular diagnostics in the local laboratories 2.Reorganization of existing processes to fulfill the standards for molecular diagnostics 3.Creation of a new Laboratory for molecular diagnostics of viral Hepatitis in Rio Branco 4.Development and Installation of missing analyzes 5.Teaching of physicians and laboratory technicians locally and in Salvador PERSPECTIVES (2) : • Relaunch new collaborative extended LIA project • Fiocruz (Porto Velho) with new partners • Merieux Foundation from Brazil/France • Pasteur Institute • Further elucidate role of small monkeys in HDV transmission • Attempt to develop HBV and HBV/HDV co-infection small primate models Remerciements Equipe Alan Kay (INSERM- U1052) Christian Trépo (INSERM-U1052) Raymundo Paraná (HUPES/UFBA) Patients Nord Nord-est Financements Rio Branco (AC) Salvador (BA) Porto Velho (RO) Muito obrigado por sua atenção!