Hepatitis C virus infection in Argentina: Burden of chronic disease

AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCVrelated morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed: (1) increased sustained virologic response (SVR); and (2) increased SVR and treatment. RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liverrelated deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Hospital Universitario Austral.; Argentina. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Bessone, Fernando. Universidad Nacional de Rosario; ArgentinaFil: Daruich, Jorge R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Estes, Chris. Center For Disease Analysis; Estados UnidosFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Razavi, Homie. Center For Disease Analysis; Estados UnidosFil: Villamil, Federico. Hospital Británico de Buenos Aires; ArgentinaFil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral.; Argentin

The Argentine experience with human immune deficiency virus positive patients in the waiting list for liver transplantation: preliminary analysis

Previamente, la seropositividad para el virus de la inmunodeficiencia humana (HIV) era una contraindicación absoluta del trasplante. Sin embargo, reportes de la época posterior al tratamiento antirretroviral altamente activo (HAART) demostraron que los resultados no se diferenciarían de la población HIV negativa. Objetivo. Evaluar la experiencia en Argentina con pacientes HIV positivos incluidos en lista para trasplante hepático. Pacientes y métodos. Se incluyeron 52 pacientes HIV positivos ingresados en lista del 12 de julio de 2005 al 31 de marzo de 2010. Los resultados se compararon con 462 pacientes HIV negativos incluidos en lista durante el mismo período. Los datos se obtuvieron del SINTRA y centros intervinientes. Resultados. La etiología de hepatopatía en el grupo HIV positivo fue: hepatitis C en 40 pacientes, hepatitis B en 3, hepatitis fulminante en 3, alcohol en 2, retrasplante en 2 y otras en 2. El MELD promedio del grupo HIV positivo al ingreso en la lista fue 16,15 (menor de 19 en 40 pacientes, mayor de 19 en 8 y emergencia en 3) y el del grupo HIV negativo fue 16,64 (NS). La evolución en lista de espera para los pacientes HIV positivos y negativos fue respectivamente: muerte en lista 14 pacientes (27%) vs 61 (18,7%) (P < 0,05), trasplante con donante cadavérico 10 (13%) vs 95 (29,4%) (P < 0,01), trasplante con donante vivo 0 (0%) vs 5 (1,1%) (NS), tiempo medio desde el ingreso en lista a la muerte 270,70±298,11 días vs 267,29±266,53 días (NS), tiempo medio en la lista hasta el trasplante 70,26±74,05 vs 261±187,6 días (P < 0,01), MELD medio al fallecimiento 12,54 (13 casos menor de 15, 1 mayor de 19) vs 19,6±9,7 (P < 0,05), y MELD medio al momento del trasplante 24,33 vs 24,1±7,6 (NS). Conclusión. Los resultados del trasplante en pacientes HIV positivos son buenos. Sin embargo, presentan muy alta mortalidad en lista de espera que no correlaciona con su gravedad medida por el score de MELD. Quienes acceden al trasplante lo hacen rápidamente en el contexto de una descompensación, por hepatitis fulminante o por retrasplante.After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. Objective. To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. Patients and methods. We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. Results. The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 16.15 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27%) vs 61 (18.7%) (P < 0.05), cadaveric donor transplant 10 (13%) vs 95 (29.4%) (P < 0.001), living donor transplant 0 (0%) vs 5 (1.1%) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). Conclusion. HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.Fil: Villamil, Alejandra. Hospital Italiano; ArgentinaFil: Bisignano, Liliana. Incucai; ArgentinaFil: Orozco, Federico. Hospital Italiano de la Plata; ArgentinaFil: Bandi, Juan Carlos. Hospital Italiano de la Plata; ArgentinaFil: Barcán, Laura. Hospital Italiano de la Plata; ArgentinaFil: McCormack, Lucas. Hospital Alemán; ArgentinaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Santibañes, Eduardo. Hospital Italiano de la Plata; ArgentinaFil: Gadano, Adrián. Hospital Italiano de la Plata; Argentin

Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children

Background: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. Methods: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. Results: sFas was associated with fibrosis severity in pediatric (significant fibrosis p=0.03, advanced fibrosis p=0.01) and adult patients (advanced fibrosis p=0.02). M30 levels were elevated in pediatric patients with severe steatosis (p=0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p=0.03) and they were associated with hepatitis severity (p=0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). Conclusions: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.Fil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casciato, Paola. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Galoppo, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Galdame, Omar. Hospital Italiano; ArgentinaFil: Galoppo, María Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Mullen, Eduardo. Hospital Italiano; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Hepatitis C Virus Diversification in Argentina: Comparative Analysis between the Large City of Buenos Aires and the Small Rural Town of O’Brien

The estimated prevalence of HCV infection in Argentina is around 2%. However, higher rates of infection have been described in population studies of small urban and rural communities. The aim of this work was to compare the origin and diversification of HCV-1b in samples from two different epidemiological scenarios: Buenos Aires, a large cosmopolitan city, and O´Brien, a small rural town with a high prevalence of HCV infection. PATIENTS AND METHODS: The E1/E2 and NS5B regions of the viral genome from 83 patients infected with HCV-1b were sequenced. Phylogenetic analysis and Bayesian Coalescent methods were used to study the origin and diversification of HCV-1b in both patient populations. RESULTS: Samples from Buenos Aires showed a polyphyletic behavior with a tMRCA around 1887-1900 and a time of spread of infection approximately 60 years ago. In contrast, samples from ÓBrien showed a monophyletic behavior with a tMRCA around 1950-1960 and a time of spread of infection more recent than in Buenos Aires, around 20-30 years ago. CONCLUSION: Phylogenetic and coalescence analysis revealed a different behavior in the epidemiological histories of Buenos Aires and ÓBrien. HCV infection in Buenos Aires shows a polyphyletic behavior and an exponential growth in two phases, whereas that in O´Brien shows a monophyletic cluster and an exponential growth in one single step with a more recent tMRCA. The polyphyletic origin and the probability of encountering susceptible individuals in a large cosmopolitan city like Buenos Aires are in agreement with a longer period of expansion. In contrast, in less populated areas such as O´Brien, the chances of HCV transmission are strongly restricted. Furthermore, the monophyletic character and the most recent time of emergence suggest that different HCV-1b ancestors (variants) that were in expansion in Buenos Aires had the opportunity to colonize and expand in O´Brien.Fil: Golemba, Marcelo Darío. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.;Fil: Culasso, Andrés Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.. Cat. de Virologia;Fil: Villamil, Federico. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad En Red El Cruce Dr. Nestor Carlos Kirchner Samic;Fil: Baré, Patricia. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Medicina Experimental;Fil: Gadano, Adrián Carlos. Htal.italiano;Fil: Ridruejo, Ezequiel. Centro de Educaciones Medicas E Investig.clinica "norberto Quirno";Fil: Martínez, Alfredo. Centro de Educaciones Medicas E Investig.clinica "norberto Quirno";Fil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.. Cat. de Virologia;Fil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.

Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations

BACKGROUND: The global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations. RESULTS: DNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008). CONCLUSIONS: These results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.Fil: Pontoriero, Ana Cecilia. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hulaniuk, María Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fortuny, Lisandro. Hospital Italiano; ArgentinaFil: Burgos Pratx, Leandro. Hospital Italiano; ArgentinaFil: Frías, Analía. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Torres, Oscar. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Nuñez, Félix. Hospital Italiano; ArgentinaFil: Gadano, Adrián. Hospital Italiano; ArgentinaFil: Argibay, Pab lo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentin

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

AIM: To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION: In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes.Fil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Borzi, Silvia Mabel. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Dirchwolf, Melisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Ridruejo, Ezequiel. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Bessone, Fernando. Sanatorio del Parque. Unidad de Hepatología; ArgentinaFil: Sirotinsky, María Ester. Hepatosur group; ArgentinaFil: Giunta, Diego Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Olivera Sendra, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Galdame, Omar Andres. Hospital Italiano; ArgentinaFil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral; Argentina. Hospital Italiano; ArgentinaFil: Fainboim, Hugo. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.Fil: Piñero, Federico. Hospital Universitario Austral; Argentina. Sanatorio de la Trinidad San Isidro; ArgentinaFil: Pages, Josefina. Hospital Universitario Austral; ArgentinaFil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Fernández, Nora. Hospital Británico de Buenos Aires; ArgentinaFil: Silva, Jorge. Provincia de San Juan. Hospital Rawson; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Zerega, Alina. Sanatorio Allende; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: D'amico, Claudia. Centro Especialidades Médicas Ambulatorias Mar del Plata; ArgentinaFil: Gaite, Luis. Clínica de Nefrología de Santa Fe; ArgentinaFil: Bermúdez, Carla. Hospital Italiano; ArgentinaFil: Cobos, Manuel. Hospital Alemán; ArgentinaFil: Rosales, Carlos. Provincia de San Juan. Hospital Rawson; ArgentinaFil: Romero, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: McCormack, Lucas. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reggiardo, Virginia. Gobierno de Santa Fe. Hospital Provincial del Centenario; ArgentinaFil: Colombato, Luis. Hospital Británico de Buenos Aires; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Silva, Marcelo. Hospital Universitario Austral; Argentin

Inesperada alta frecuencia de infección por el virus de la hepatitis E en pacientes cirróticos alcohólicos de Argentina

El virus de la Hepatitis E (HEV) es un virus ARN de simple cadena de trasmisión entérica y zoonótico, frecuentemente asociado a hepatitis agudas autolimitadas. Recientemente, se describió la progresión a cronicidad en pacientes inmunosuprimidos y la cirrosis ha sido postulada como un factor predisponente a la infección por HEV. En Argentina, se ha reportado la circulación de HEV genotipo 3 en cerdos y matrices acuosas y una seroprevalencia de anticuerpos anti-HEV entre 1,8 y 16% en población general y donantes de sangre. Además, se reportaron seroprevalencias mayores (6 – 35%) en pacientes hemodializados, trasplantados de órganos sólidos y en individuos HIV+, siendo escasas las evidencias de HEV en pacientes cirróticos. El objetivo del trabajo fue describir la frecuencia de infección de HEV y factores asociados en pacientes cirróticos de Argentina. El diagnóstico de HEV se realizó detectando IgM e IgG anti-HEV por ELISA y ARN por PCR en tiempo final, en muestras de suero obtenidas de 3 centros de salud de Córdoba y Buenos Aires (n=122). La prevalencia global de IgG anti-HEV en pacientes cirróticos fue de 22,1% (27/122). El 70,4% de los IgG anti-HEV positivos fueron individuos alcohólicos, existiendo asociación estadísticamente significativa entre cirrosis alcohólica e infección por HEV (p&lt;0,05). Se detectó IgM en el 51,8% (14/27) de los pacientes IgG anti-HEV (+) y ARN HEV en 2 de ellos. Los resultados muestran una inesperada alta prevalencia de HEV en este grupo de pacientes adultos cirróticos alcohólicos argentinos. Se necesitan más estudios para dilucidar si la cirrosis alcohólica sería un factor predisponente para la infección por HEV, o si la infección (crónica) por HEV induciría la progresión a cirrosisFil: Fantilli, Anabella. Universidad Nacional de CórdobaFil: Pisano, María Belén. Buenos Aires (Argentina). Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).Fil: Zárate, Fabián.Fil: Trinks, Julieta. Buenos Aires (Argentina). Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).Fil: Marciano, Sebastián.Fil: Balderramo, Domingo.Fil: Fernando, Diehl.Fil: Martínez Wassaf, Maribel.Fil: Haddad, Leila.Fil: Gadano, Adrián.Fil: Debes, José.Fil: Ré, Viviana

Plasma and stool metabolomic biomarkers of non-alcoholic fatty liver disease in Argentina

Background: Non-invasive biomarkers are urgently needed to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk of disease progression, particularly in high prevalence areas such as Latin America. In this regard, targeted metabolomics is a powerful technology for discovering new gut microbiome-derived metabolites. Thus, we aimed to identify potential metabolomic biomarkers related to NAFLD stage in Argentina, and to assess their relationship with clinical and host genetic factors. Methods: Adult healthy volunteers (HV) and biopsy-proven simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) patients were recruited. Demographic, clinical and food frequency consumption data, as well as plasma and stool samples were collected. SNP rs738409 (PNPLA3 gene) was determined in all volunteers. HPLC and flow injection analysis with MS/MS in tandem was applied for metabolomic studies using the MxP Quant 500 Kit (Biocrates Life Sciences AG, Austria). Significantly different metabolites among groups were identified with MetaboAnalyst v4.0. Bivariate and multivariate analyses were used to identify variables that were independently related to NAFLD stage. Forward stepwise logistic regression models were constructed to design the best feature combination that could distinguish between study groups. Receiver Operating Characteristic (ROC) curves were used to evaluate models? accuracy.Results: 19 HV, 12 SS and 22 NASH patients were recruited. Diet was similar between groups. The concentration of 33 out of 424 detected metabolites (25 in plasma and 8 in stool) was significantly different among study groups. Levels of triglycerides (TG) were higher among NAFLD patients, whereas levels of phosphatidylcholines (PC) and lysoPC were higher among HV. The PNPLA3 risk genotype for NAFLD and NASH (GG) was related to higher plasma levels of eicosenoic acid FA(20:1) (p<0.001). Plasma metabolites showed a higher accuracy for diagnosis of NAFLD and NASH when compared to stool metabolites (Table 1). Body mass index (BMI) and plasma levels of PC aa C24:0, FA(20:1) and TG(16:1_34:1) showed high accuracy for diagnosis of NAFLD; whereas the best AUROC for discriminating NASH from SS was that of plasma levels of PC aa C24:0 and PC ae C40:1 (Table 1).Conclusions: Gut microbiome-derived metabolomic biomarkers were identified in plasma and stool, but plasma metabolites were better diagnostic biomarkers of NAFLD and NASH in Argentina. Further validation studies are needed.Fil: Mazzini, Flavia Noelia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Cook, Frank. Novartis Institutes For Biomedical Research; Estados UnidosFil: Gounarides, John. Novartis Institutes For Biomedical Research; Estados UnidosFil: Marciano, Sebastian. Hospital Italiano; ArgentinaFil: Haddad, Leila. Hospital Italiano; ArgentinaFil: Tamaroff, Ana Jesica. Hospital Italiano; ArgentinaFil: Casciato, Paola. Hospital Italiano; ArgentinaFil: Narvaez, Adriana Haydée. Hospital Italiano; ArgentinaFil: Mascardi, María Florencia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Orozco, Federico. Hospital Alemán; ArgentinaFil: Quiroz, Nicolas. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Risk, Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Gutt, Susana. Hospital Italiano; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Mendez Garcia, Celia. Hospital Italiano; ArgentinaFil: Marro, Martin. Novartis Institutes For Biomedical Research; Estados UnidosFil: Penas Steinhardt, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaThe Liver Meeting Digital ExperienceEstados UnidosAmerican Association for the Study of the Liver Diseas

Translational research in microbiome (intramic): an area of common and growing interest at imtib, hospital italiano and instituto universitario

Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso.It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother’s skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project “Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents”. At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research.Fil: Vaccaro, Carlos Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano de Buenos Aires; ArgentinaFil: Risk, Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Figari, Marcelo Fernando. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Llesuy, Susana Francisca. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piñero, Tamara Alejandra. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Burgos, Valeria Laura. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Mazzini, Flavia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Alberbide, Jorge. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Basqueira, Ana. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Giménez, María Isabel. No especifíca;Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Arguero, Julieta. Hospital Italiano; Argentin