HEPATITIS

RESUMEN

Se estima que aproximadamente 250 millones de personas en el mundo están infectadas por el virus de la hepatitis B y 150 millones por el virus de la hepatitis C, generando más de un millón de muertes anuales debido a sus consecuencias: cirrosis y carcinoma hepatocelular. Afortunadamente los tratamientos para la hepatitis C han mejorado en forma espectacular en los últimos años debido al mejor entendimiento de los mecanismos de replicación del virus que han posibilitado el desarrollo de antivirales potentes y seguros. Nuestro grupo se ha dedicado al estudio de los mecanismos traduccionales del virus de la hepatitis C, la replicación extrahepática del virus y su cercana relación con el metabolismo lipídico. Adicionalmente, se ha contribuido a un mejor entendimiento de la epidemiología de estas infecciones, al estudiar datos de prevalencia, respuesta a terapia y contribuir a la generación de guías de tratamiento nacionales y regionales.

PROYECTOS

(2016 – 2018, FONIS, Soza A, Investigador Principal)

Prevalence of hepatitis B, hepatitis C and human immunodeficiency virus (HIV) in prospective blood donors deferred because of risk behaviors.

(2013 – 2016, FONDECYT N° 1130357, Soza A, Co-Investigador, M López-Lastra, Co-Investigador)

Hepatitis C virus exploits the hepatic lipid pathways: Role of NPC1L1 in HCV infection.

(2008 – 2011, FONDECYT N° 1080323, Soza A, Co-Investigador, M López-Lastra, Co-Investigador)

Role of extrahepatic replication of hepatitis C virus in the prediction of response to antiviral therapy.

(2007 – 2009, FONIS, Soza A, Investigador Principal)

Evaluation of Results of the Pilot Program of Hepatitis C Treatment.

(2005 – 2007, FONDECYT N° 1050782, Soza A, Co-Investigador, M López-Lastra, Co-Investigador)

Role of extrahepatic viral replication on the natural history and clinical manifestations of chronic hepatitis C.

PUBLICACIONES SELECCIONADAS

Vargas C, Espinoza MA, Giglio A, Soza A. “Estudio de impacto presupuestal de Daclatasvir asociado a Asunaprevir para el tratamiento de la Hepatitis C desde la perspectiva del sistema de salud público chileno”. Value in Health Regional Issues. 2017. 14:28-32.

Monrroy H, López-Lastra M, Soza A. “Hepatitis C virus may have an entero-hepatic cycle which could be blocked with ezetimibe”. Med Hypotheses. 2017 May;102:51-55.

Monrroy H, Angulo J, Pino K, Labbé P, Miquel JF, López-Lastra M, Soza A. “Detection of high biliary and fecal viral loads in patients with chronic hepatitis C virus infection”. Gastroenterol Hepatol. 2017 May;40(5):339-347.

Monrroy-Bravo H, Angulo J, Pino K, Labbé P, López-Lastra M, Soza A. “Effect of ezetimibe in HCV viral load after liver transplantation.” Ann Hepatol. 2016. Sep-Oct;15(5):803-5.

Dore GJ, Conway B, Luo Y, Janczewska E, Knysz B, Liu Y, Streinu-Cercel A, Caruntu FA, Curescu M, Skoien R, Ghesquiere W, Mazur W, Soza A, Fuster F, Greenbloom S, Motoc A, Arama V, Shaw D, Tornai I, Sasadeusz J, Dalgard O, Sullivan D, Liu X, Kapoor M, Campbell A, Podsadecki T. “Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials”. J Hepatol. 2016 Jan;64(1):19-28.

Ruiz A, Soza A. “Tratamiento de la hepatitis C en cirrosis: beneficios y riesgos”. Gastr Latinoam 2016; Vol 27, Supl Nº 1: S 64-S 68.

Vargas CL, Espinoza MA, Giglio A, Soza A. “Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis C Genotype 1b Naïve Patients in Chile”. PLoS One. 2015 Nov 6;10(11):e0141660.

*Rivera MM, *Soza A, Jazwinski A, Mi L, Kleiner DE, Zhao X, Zuber C, Brust D, Hsu E, Simpson J, Hoofnagle JH, Heller T. “HIV Through the looking glass: Insights derived from hepatitis B”. J Acquir Immune Defic Syndr. 2015 Feb 1;68(2):123-7. (*Contributed equally).

Soza A, Labbé P, Arrese M, Riquelme A, Barrera F, Benítez C, Huete A, Balcells ME, Labarca J. “Mycobacterium abscessus pulmonary infection during hepatitis C treatment with telaprevir, peginterferon and ribavirin”. Ann Hepatol. 2015. Jan-Feb;14(1):132-6.

Méndez-Sánchez N, Paraná R, Cheinquer H, Alves de Mattos A, Gadano A, Silva M, Pessôa MG, Gomes-Ferraz ML, Soza A, Mendes-Correa MC, Chávez-Tapia NC, Dagher L, Padilla M, Hernandez N, Sánchez-Avila JF, Contreras F, Moraes-Coelho HS, Parise ER, Bessone F, Uribe M. “Latin American Association for the Study of the Liver: Recommendations on treatment of hepatitis C”. Ann Hepatol. 2014 Aug;13 Suppl 2:1-66.

Soza A, Lopez-Lastra M. “IL28B Polymorphisms Among Latin American HCV Patients”. Curr Hepatitis Rep. 2013;12:276–279.

Chávez-Tapia NC, Ridruejo E, Alves de Mattos A, Bessone F, Druich J, Sánchez-Avila JF, Cheinquer H, Zapata R, Uribe M, Bosques-Padilla F, Gadano A, Soza A, Dávalos-Moscol M, Marroni C, Muñoz-Espinoza L, Castro-Narro G, Paraná R, Méndez-Sánchez N. “An update on the management of hepatitis C: guidelines for protease inhibitor-based triple therapy from the Latin American Association for the Study of the Liver”. Ann Hepatol. 2013;12(2):S3-S35.

Angulo J, Pino K, Pavez C, Biel F, Labbé P, Miquel JF, Soza A, López-Lastra M. “Genetic variations in host IL28B links to the detection of peripheral blood mononuclear cells-associated hepatitis C virus RNA in chronically infected patients”. J Viral Hepat. 2013 Apr;20(4):263-72.

Soza A. “Hepatitis C RNA clearance after treatment with ezetimibe”. Liver Int. 2012;32(8):1323-4.

Manns MP, Gane E, Rodriguez-Torres M, Stoehr A, Yeh CT, Marcellin P, Wiedmann RT, Hwang PM, Caro L, Barnard RJ, Lee AW; for the MK-7009 Protocol 007 Study Group. “Vaniprevir with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis C – a randomized phase 2 study”. Hepatology. 2012 56(3):884-893.

Soza A. “Aproximación al paciente con hepatitis C que ha fallado al tratamiento antiviral”. Gastr Latinoam 2011; Vol 22, Nº 2: 148-151.

Arrese M, Riquelme A, Soza A. “Insulin resistance, hepatic steatosis and hepatitis C: a complex relationship with relevant clinical implications”. Ann Hepatol. 2010;9 Suppl:112-118.

Soza A, Riquelme A, Arrese M. “Routes of transmission of hepatitis C virus”. Ann Hepatol. 2010;9 Suppl:30-33.

Latin American Association for the Study of the Liver. “Latin American Association for the Study of the Liver Practice Guidelines. Diagnosis, management, and treatment of hepatitis C”. Ann Hepatol. 2010;9 Suppl:8-26.

Barrera F, Soza A. “Shortened therapy for genotype 1 hepatitis C virus. The final answer?” Ann Hepatol. 2010;9(1):112-3.

Rotman Y, Borg BB, Soza A, Feld JJ, Modi AA, Loomba R, Lutchman G, Rivera E, Doo E, Ghany MG, Heller T, Neumann AU, Liang TJ, Hoofnagle JH. “Clinical trial: low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3 – efficacy, tolerability, viral kinetics and cytokine response”. Aliment Pharmacol Ther. 2010; 31(9):1018-27.

Caneo C, González M, Repetto P, Soza A. “Trastornos psiquiátricos y cognitivos de la hepatitis C y su tratamiento con interferón”. Rev Med Chile 2010;138:1431-40.

Soza A, San Martín AM, Jofré L, Noriega LM, Hunter B, Muñoz G, Becerra M, Martínez MC, Soto K, Rivera M, Tohá D. “Guía clínica de manejo de la infección por virus de la Hepatitis C”. Gastr Latinoam 2010;21(3):379-409.

Vera-Otarola J, Barría MI, León U, Carvallo P, Soza A, López-Lastra M. “Is single-strand conformation polymorphism analysis of the full 5’untranslated region an adequate approach to study hepatitis C virus quasispecies distribution?” Journal of Virology. 2009;83(17):9018-21.

Vera-Otarola J, Barrıa MI, Leon U, Marsac D, Carvallo P, Soza A, Lopez-Lastra M. “Hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cells of treatment naïve chronically infected patients”. J Viral Hepat. 2009;16(9):633-43.

Barrıa MI, Gonzalez A, Vera-Otarola J, Leon U, Vollrath V, Marsac D, Monasterio O, Perez-Acle T, Soza A, Lopez-Lastra M. “Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role on cap-independent translation”. Nucleic Acids Research. 2009;37(3):957-71.

Barría MI, Vera-Otarola J, León U, Vollrath V, Marsac D, Riquelme A, López-Lastra M, Soza A. “Influence of extrahepatic viral infection on the natural history of hepatitis C”. Ann Hepatol. 2008;7:136-43.

Soza A, López-Lastra M. “Hepatitis C en Chile: Magnitud del problema”. Rev Med Chil. 2006;134:777-88.

Soza A, Heller T, Ghany M, G, Liang J, Germain J, Hsu HH, Park Y, Hoofnagle JH. “Pilot study of interferon gamma for chronic hepatitis C”. J Hepatol. 2005;43:67-71.

González R, Soza A, Hernández V, Pérez RM, Alvarez M, Morales A, Arrellano M, Riquelme A, Viviani P, Covarrubias C, Arrese M, Miquel JF, Nervi F. “Incidence and prevalence of hepatitis C virus infection in Chile”. Ann Hepatol. 2005;4:127-30.

Soza A, Arrese M, González R, Alvarez M, Pérez RM, Cortés P, Patillo A, Riquelme A. “Clinical and epidemiological features of 147 Chilean patients with chronic hepatitis C”. Ann Hepatol. 2004;3:146-51.

Riquelme A, Soza A, Nazal L, Martínez G, Kolbach M, Patillo A, Arellano JM, Duarte I, Martínez J, Molgó M, Arrese M. “Histological resolution of steatohepatitis after iron depletion”. Dig Dis Sci. 2004;49:1012-5.

Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. “A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis”. Hepatology. 2004;39:188-96.

Hoofnagle JH, Ghany MG, Kleiner DE, Doo E, Heller T, Promrat K, Ong J, Khokhar F, Soza A, Herion D, Park Y, Everhart JE, Liang TJ. “Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin”. Hepatology. 2003;38:66-74.

Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ. “Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C”. Gastroenterology. 2003;124:352-360.

Soza A, Lau DT, Khokhar MF, Conjeevaram H, Park Y, Hoofnagle JH. “Resolution of chronic hepatitis B-associated autoimmune neutropenia with alpha interferon therapy”. J Pediatr Gastroenterol Nutr. 2003;36:141-3.

Soza A, Everhart J, Ghany M, Doo E, Heller T, Promrat K, Park Y, Liang J, Hoofnagle JH. “Neutropenia associated with alpha interferon therapy of chronic hepatitis C”. Hepatology. 2002;36:1273-1279.