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Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients.To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC.Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow-up.Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models.Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

espanolIntroduccion: La hemocromatosis hereditaria es una enfermedad genetica que genera una sobrecarga sistemica de hierro, y en etapas avanzadas, puede afectar el corazon. El compromiso miocardico precoz por esta enfermedad no ha sido suficientemente investigado. Objetivo: Comparar mediante ecocardiografia Doppler convencional y strain 2D un grupo de pacientes con diagnostico reciente de hemocromatosis hereditaria vs. un grupo control. Material y metodos: Se estudiaron pacientes con diagnostico reciente de hemocromatosis hereditaria, no tratados. Se les realizo un ecocardiograma Doppler convencional y con strain bidimensional para evaluar la deformacion longitudinal, radial y circunferencial, y el giro y torsion del ventriculo izquierdo. Resultados: Participaron 23 varones con hemocromatosis hereditaria (46 ± 18 anos) y 20 sujetos control (45 ± 15 anos). No hubo diferencias en los espesores y tamanos ventriculares. Los pacientes con hemocromatosis hereditaria tuvieron una fraccion de eyeccion del ventriculo izquierdo menor (59 ± 4% vs. 62 ± 4 %; p = 0,01). No hubo diferencias en cuanto a ESPAM, TAPSE u onda s´ del ventriculo izquierdo. Se observo una disminucion significativa del strain en los pacientes con HH, con mayor compromiso de la deformacion radial (37 ± 12 % vs. 55 ± 17 %; p = 0,01) y circunferencial (−19,5 ± 2,8 % vs. −22,5 ± 2,8 %; p = 0,001), y, en menor medida, de la longitudinal (−19 ± 1,8 % vs. −21,1 ± 2,5 %; p=0,04). Tambien este grupo tuvo menor rotacion apical, menor giro (17,7 ± 13° vs. 25 ± 7°; p = 0,03) y menor torsion (2,3 ± 1,8 °/cm vs. 3,3 ± 1,1 °/cm; p = 0,03). No hubo correlacion entre los diferentes tipos de deformacion y los parametros bioquimicos del metabolismo ferrico. Conclusiones: La ecocardiografia y especialmente la evaluacion del strain 2D es capaz de detectar de manera temprana ligeras alteraciones de la mecanica ventricular en pacientes asintomaticos, con sobrecarga sistemica de hierro por hemocromatosis hereditaria. EnglishBackground: Hereditary hemochromatosis is a genetic disorder characterized by systemic iron overload which can involve the heart in advanced stages. Early myocardial involvement has not been thoroughly investigated. Objective: The aim of our study was to evaluate the performance of conventional Doppler-echocardiography and 2D strain echocardiography in a group of patients with newly diagnosed hereditary hemochromatosis vs. a control group. Methods: Patients with newly diagnosed hereditary hemochromatosis without treatment were included. All the patients underwent conventional Doppler echocardiography and 2D strain echocardiography with evaluation of left ventricular longitudinal, radial and circumferential strain, twist and torsion. Results: Twenty-three male patients with hereditary hemochromatosis (46±18 years) and 20 male controls (45±15 years) were included. There were no differences in ventricular dimensions and wall thickness. Left ventricular ejection fraction was lower in patients with hereditary hemochromatosis (59±4% vs. 62±4%; p=0.01). There were no differences in MAPSE, TAPSE and left ventricular s’ velocity. There was a significant decrease in global strain in patients with hereditary hemochromatosis, with greater involvement of radial strain (37±12 % vs. 55±17%; p=0.01) and circumferential strain (-19.5±2.8% vs. -22.5±2.8%; p=0.001), and less involvement of longitudinal strain (-19±1.8% vs. -21.1±2.5%; p=0.04). Myocardial rotation showed lower twist (17.7±13° vs. 25±7°; p=0.03) and lower torsion (2.3±1.8°/cm vs. 3.3±1.1 °/cm; p=0.03). There was no correlation between the different strain parameters and iron metabolism. Conclusions: Echocardiography, and particularly 2D strain analysis can detect early abnormalities of ventricular mechanics in asymptomatic patients with systemic iron overload due to hereditary hemochromatosis

Goals:We aim to describe the efficacy, safety profile, and variables associated with survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib in South America.Background:Sorafenib has been shown to improve survival in patients with advanced HCC. There are few data on sorafenib use for HCC in South America.Study:We performed a retrospective analysis of HCC cases treated with sorafenib from 8 medical centers in 5 South American countries, between January 2010 and June 2017. The primary endpoint was overall survival (OS), which was defined as time from sorafenib initiation to death or last follow-up. Risk factors for decreased OS were assessed using Cox proportional hazard regression and log-rank tests.Results:Of 1336 evaluated patients, 127 were treated with sorafenib and were included in the study. The median age of individuals was 65 years (interquartile range, 55 to 71) and 70% were male individuals. Median OS in all patients was 8 months (interquartile range, 2 to 17). Variables associated with survival on multivariate analysis were platelets >//

BackgroundHereditary Hemochromatosis (HH) is a genetic condition associated with a systemic iron overload. Heart failure is an important cause of mortality. It has been demonstrated early stages of systolic and diastolic left ventricular dysfunction in previous studies. The aim of the study is to compare the left atrial (LA) function between asymptomatic HH patients and a control group using 2D speckle tracking.MethodsProspective study. LA strain, LA strain rate and LA volumetric parameters during the reservoir, conduit and contraction phases were studied. The LA Stiffness Index was calculated by the ratio between E/e and LA reservoir strain.Results30 patients with HH (90% males, 47 ± 18 years old) and 30 healthy controls (85% males, 45 ± 13 years old) were included. LA volume was similar in both groups. No differences were observed in LA ejection fraction (EF), LA passive EF and LA active ejection fraction between both groups. On the contrary, the HH group had lower LA strain during the reservoir (31.5 ± 6.5% vs 38.3 ± 7.9%; p = 0.002), and conduit phases (-18 ± 7% vs -23.3 ± 6.4%; p = 0.01) and lower LA conduit strain rate (-1.7 ± 0.7 seg− 1 vs -2.1 ± 0.5 seg− 1; p = 0.02) than controls. The LA stiffness index was significantly higher in the HH group (0.25 ± 0.9 vs 0.19 ± 0.6; p = 0.01).ConclusionsEarly abnormalities in the LA function could be detected by using 2D speckle tracking study despite no evidence of changes in atrial size or volumetric parameters.

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6% (CI 3.7–5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14−25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9−4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). Conclusions: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIFC had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380. Fil: Mendizabal, Manuel. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Ridruejo, Ezequiel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Centro de Educación Médica e Investigaciones Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Piñero, Federico. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Anders, Margarita. Hospital Alemán; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Padilla, Martín Jesus. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Toro, Luis G.. Fundación de Medellín y Rionegro; Colombia Fil: Torre, Aldo. Instituto Nacional de Ciencias Médicas y Nutrición; México Fil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; Argentina Fil: Urzúa, Alvaro. Universidad de Chile; Chile Fil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Silveyra, María Dolores. Sanatorio Anchorena; Argentina Fil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Peralta, Mirta. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Pages, Josefina. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: García, Sandro Ruiz. Hospital de Víctor Lazarte Echegaray; Perú Fil: Gutierrez Lozano, Isabel. Centro Médico ABC; México Fil: Macias, Yuridia. IMSS Hospital General Regional No. 1 “Dr. Carlos Mc Gregor Sánchez”; México Fil: Cocozzella, Daniel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Hospital Italiano de La Plata; Argentina Fil: Chavez Tapia, Norberto. Medica Sur Clinic & Foundation; México Fil: Tagle, Martín. Clínica Anglo-Americana; Perú Fil: Dominguez, Alejandra. Hospital Padre Hurtado; Chile Fil: Varón, Adriana. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Fundación Cardio Infantil; Colombia Fil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo del IESS; Ecuador Fil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga”; México Fil: Bustios, Carla. Fundación Cardio Infantil; Colombia Fil: Conte, Damián. Hospital Privado de Córdoba; Argentina Fil: Escajadillo, Nataly. Universidad Austral; Argentina Fil: Rubinstein, Fernando Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Tenorio, Laura. Hospital Nacional Edgardo Rebagliati Martins; Perú

Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease, with an estimated prevalence of 20-30% in the general population and increased to 60-80% in risk groups. It encompasses the spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to variable degrees of fibrosis, cirrhosis and all its complications. It is associated with cardiovascular, neoplasm and liver mortality, requiring a multidisciplinary approach. A change in the entity name has recently been suggested and a group of experts has proposed calling it Metabolic (dysfunction) Associated Fatty Liver Disease (MAFLD). This name has not yet been accepted and has generated significant controversy. Due to the increase in its prevalence, nonalcoholic fatty liver disease has become a relevant health problem that requires specific actions for its detection, diagnosis, monitoring and treatment. Identifying patients at risk of progressing to more severe forms is essential but not too easy. Patients with nonalcoholic steatohepatitis should be identified; mainly those with fibrosis, the most important characteristic associated with mortality. The main treatment for all stages of the disease consists of lifestyle interventions and aggressive correction of comorbidities. Other therapies, such as treatment with pioglitazone or GLP-1RA, should be selected and used in patients with nonalcoholic steatohepatitis who are at higher risk of progression of liver and cardiovascular disease, like obese and type 2 diabetic patients.

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the impact of SARS-CoV-2 infection on clinical outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6%(CI 3.7-5.6) subjects had cirrhosis (n=96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis compared to 16% in those without cirrhosis (P30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P

Introduction & objectives: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. Materials & methods: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. Results: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7–47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4–16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9–21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1–14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1–2.0); P = 0.01], and severe COVID-19 (2.6 [2.0–3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. Conclusions: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. Fil: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; Argentina Fil: 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; Argentina Fil: Anders, Margarita. Hospital Aleman; Argentina Fil: Silveyra, María Dolores. Sanatorio Anchorena; Argentina Fil: Torre, Aldo. Centro Médico ABC; México Fil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; Perú Fil: Urzúa, Alvaro. Hospital Clínico de la Universidad de Chile; Chile Fil: Pages, Josefina. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Toro, Luis G.. Hospitales de San Vicente Fundación de Medellín y Rionegro; Colombia Fil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Miranda Zazueta, Godolfino. Instituto Nacional de Ciencias Médicas y Nutrición; México Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Gutiérrez, Isabel. Centro Médico ABC; México Fil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Venturelli, Maria Grazia. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Varón, Adriana. Fundación Cardio-Infantil; Colombia Fil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo; Ecuador Fil: Tagle, Martín. Clínica Anglo-Americana; Perú Fil: García, Matías. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Tassara, Alfredo. Hospital Aleman; Argentina Fil: Brutti, Julia. Sanatorio Anchorena; Argentina Fil: Ruiz García, Sandro. Hospital de Víctor Lazarte Echegaray; Perú Fil: Bustios, Carla. Clínica Delgado; Perú Fil: Escajadillo, Nataly. Hospital Nacional Almanzor Aguinaga Asenjo; Perú Fil: Macias, Yuridia. No especifíca; Fil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga"; México Fil: Gómez, Andrés J.. Hospital Universitario Fundación Santa Fé de Bogotá; Colombia Fil: Dominguez, Alejandra. Hospital Padre Hurtado; Chile Fil: Castillo Barradas, Mauricio. Hospital de Especialidades del Centro Médico Nacional La Raza; México Fil: Contreras, Fernando. No especifíca; Fil: Scarpin, Aldana. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Schinoni, Maria Isabel. Hospital Alianza; Brasil Fil: Toledo, Claudio. Universidad Austral de Chile; Chile Fil: Girala, Marcos. Universidad Nacional de Asunción; Paraguay Fil: Mainardi, Victoria. Hospital Central De las Fuerzas Armadas; Uruguay Fil: Sanchez, Abel. Hospital Roosevelt; Guatemala Fil: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina Fil: Rubinstein, Fernando Adrian. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral; Argentina

Our aim was to analyze the effect of circulating triglyceride rich lipoprotein (TRL) on endothelial function in metabolic syndrome (MetS). Methods We studied 40 patients with MetS (ATPIII), divided into those presenting normal endothelial function (n = 19) and those with endothelial dysfunction (n = 21) by means of the evaluation of pulse wave velocity, before and after brachial artery ischemia. In fasting serum we measured lipid and lipoprotein profile, insulin and glucose (HOMA-IR). Moreover, isolated TRL (d

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Sorafenib, a multi-tyrosine kinase inhibitor, remains the standard of care for patients with inoperable or advanced-stage HCC. In resource-limited settings without access to surgical or locoregional therapy, sorafenib may be the only option for treating HCC. However, due to a modest survival benefit, as well as the limiting cost of sorafenib in certain regions, appropriate selection of patients for treatment is essential. Evaluation of Barcelona Clinic Liver Cancer (BCLC) criteria in resource-limited settings is frequently unachievable due to a variety of reasons. Using a cohort from the South American liver research network (1336 HCC cases), we created a cost-effective prognostic scoring system to help identify patients likely to have a survival benefit on sorafenib treatment, using simple laboratory variable Fil: Leathers, James S.. Vanderbilt University; Estados Unidos Fil: Balderramo, Domingo. Universidad de Córdoba; España Fil: Prieto, Jhon. Centro de Enfermedades Hepáticas y Digestivas; Colombia Fil: Diehl, Fernando. Universidad de Córdoba; España Fil: Gonzalez-Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Ferreiro, Melina R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Carrera, Enrique. Hospital Eugenio Espejo; Ecuador Fil: Barreyro, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina Fil: Diaz Ferrer, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Singh, Dupinder. University of Minnesota; Estados Unidos Fil: Mattos, Angelo Z.. Universidade Federal de Ciencias Da Saúde de Porto Alegre; Brasil Fil: Carrilho, Flair. Universidade de Sao Paulo; Brasil Fil: Debes, Jose D.. University of Minnesota; Estados Unidos

In Hemochromatosis (H) iron is stored in tissues, causing organ injury and failure. Patients with H have a shorter life expectancy and an increase in CVR. Our group could prove that arterial stiffness was increased and they had added endothelial dysfunction. After that we also were able to demonstrate that both improve by reducing iron levels with phlebotomies. Due to these findings we ask how iron-overload made it (getting inside or more likely inducing inflammation). Anyway either directly or indirectly AW could be a target of iron-overload. To test this hypothesis we did an experimental correlation by using a known model of H in rats and we analize histologically the AW Twelve young rats (3 months old), an average weight of 300 gr, fed as usual, in individual cages with dark light cycles of 12 h and controlled temperature (22±3°C), were ramdonly divided in 2 groups: 1) Iron-overoload group (IOG). They were daily administrated intraperitoneally 10 mg of elemental iron (0,1 ml of dextran iron, Venofer®) 12 injections in total 2) Control group (CG) the same injections scheme but with placebo. The handlings of animals was under the norms of the bioterium and standards designed for that purpose. At the end of experimental period (8 weeks) animals were sacrificed and studied. The histoarchitecture of the proximal aortic wall (fixed in 4 % formalin, paraffin-embedded, sectioned into thin slices, H&E, Masson′s trichrome and VVG staining) showed no significant differences in the histology (H&E) between IOG and CG. No evidence of iron inside the AW. On the other hand inflammatory component was significantly increased in IOG compared to CG, perivascular lymphocyte count 5-12/0 IOG/CG, perivascular macrophages, 3-5/0 IOG/CG. Elastic fibers were not fragmented but become thin and lost their disposition in IOG. In conclusions we can affirm that AW could represent a novel target in H and could may the nexus to cardiovascular disease. The indirect mechanism (inflammation and elastic fibers) explains why previously improved after phlebotomies. Our findings supports future research including inflammatory mediators and their tissue expression, and extend them to others iron overload disorders.

Hereditary Hemochromatosis (HH) is a genetically determined disease where iron is excessively stored in tissues, causing organ injury and failure. An increase of cardiovascular risk (CVR) has been reported in HH. Part of the iron overload induces vascular fibrosis and endothelial dysfunction (ED). Therefore, arterial wall emerge as a novel organ target organ in HH. Carotid-femoral pulse wave velocity (PWV-CF) assesses arterial stiffness (AS), and has predictive value for CV events. PWV variation pre- and post-induced transient ischemia of brachial artery (PWV-CB) has been validated to evaluate ED. We hypothetized that patients with HH have an increase in PWV-CF and PWV-CB due to iron overload, and that phlebotomy by reducing iron levels decreases arterial stiffness and restores endothelial function. To test this hypothesis we assessed PWV-CF and PWV-CB in 52 patients with HH before and after phlebotomy and compare against control. PWV-CF and PWV-CB variations were assessed using Complior System (Artech-Medical, Francia). PWV-CF was significantly increased in HH patients compared to control group (8.5±1.7 m/s vs. 6.4±0.8 m/s, P

Background & Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America. Methods: We evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations. Results: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and is associated almost universally with chronic liver disease and cirrhosis. Risk factors for HCC generally vary by geographic region. To date, studies have focused on characterizing patients with HCC in Europe, North America, Asia, and, to a lesser extent, Africa.1,2 However, little is known about the underlying demographic characteristics and risk factors for HCC in South America, particularly the association between viral hepatitis and HCC. Fil: Chan, Aaron J.. University of Minnesota; Estados Unidos Fil: Balderramo, Domingo. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina Fil: Kikuchi, Luciana. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil Fil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Prieto, Jhon E.. Centro de Enfermedades Hepáticas y Digestivas, Organización Sanitas; Colombia Fil: Tapias, Monica. Organizacion Sanitas; Colombia Fil: Idrovo, Victor. Organizacion Sanitas; Colombia Fil: Davalos, Milagros B.. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Cairo, Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina Fil: Barreyro, Fernando Javier. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paredes, Mario Sebastian. Hospital Presidente Peron; Argentina Fil: Hernandez, Nelia. Universidad de la República; Uruguay Fil: Avendaño, Karla. Universidad de la República; Uruguay Fil: Diaz Ferrer, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Yang, Ju Dong. Hospital Nossa Senhora Da Conceicao; Brasil Fil: Carrera, Enrique. University of Minnesota; Estados Unidos Fil: Mattos, Angelo Z.. Hospital Nossa Senhora Da Conceicao; Brasil Fil: Hirsch, Bruno S.. Hospital Nossa Senhora Da Conceicao; Brasil Fil: Gonçalves, Pablo T.. Hospital Nossa Senhora Da Conceicao; Brasil Fil: Carrilho, Flair J.. Universidade de Sao Paulo; Brasil Fil: Roberts, Lewis R.. Hospital Nossa Senhora Da Conceicao; Brasil Fil: Debes, Jose D.. University of Minnesota; Estados Unidos

Fil: Inzaugarat, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Inzaugarat, María Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Hospital de Clínicas "José de San Martín". Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Baz, Placida. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Hospital de Clínicas "José de San Martín". Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: García, Cecilia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: García, Cecilia Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Hospital de Clínicas "José de San Martín". Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Cherñavsky, Alejandra Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Cherñavsky, Alejandra Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Hospital de Clínicas "José de San Martín". Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: De Matteo, Elena. Hospital de Niños "Dr. Ricardo Gutiérrez". Servicio de Patología; Argentina Fil: Lucero, Diego. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica. Laboratorio de Lípidos y Arterioesclerosis; Argentina Fil: González Ballerga, Esteban. Universidad de Buenos Aires. Hospital de Clínicas "José de San Martín". División de Gastroenterología; Argentina Fil: Daruich, Jorge. Universidad de Buenos Aires. Hospital de Clínicas "José de San Martín". División de Gastroenterología; Argentina Fil: Sorda, Juan Antonio. Universidad de Buenos Aires. Hospital de Clínicas "José de San Martín". División de Gastroenterología; Argentina Fil: Wald, Miriam Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Wald, Miriam Ruth. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Abstract: The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties. This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model. The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4 cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4 cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages. ur findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4 cells requires additional research.

OBJECTIVE To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. METHODS Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. RESULTS Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm2 , respectively, P

Hereditary Hemochromatosis (HH) is a genetically determined disease of iron overload with excessive tissue storage, which can lead to tissue injury, fibrosis and organ failure. Recently, an increase of cardiovascular risk (CVR) has been reported in this group. Pulse wave velocity (PWV) is the simplest way to assess arterial stiffness (AS), and has predictive value for CVevents. PWV variation preand postinduced ischemia of brachial artery has been validated to evaluate endothelial dysfunction (ED). We previously reported a significant enhanced PWV and endothelial dysfunction in 30 HH patients compared with healthy controls. Patients with HH treated with repetitive phlebotomies (standard of care for these patients) show significantly longer survival rate (5-10 years) than untreated patients. We hypothesized that phlebotomy reduces iron overload and decreases the excessive storage of this metal in the arterial wall, reducing the vascular stiffness and therefore decreasing carotid-femoral PWV. To test this hypothesis we measured carotid-femoral PWV before and after phlebotomy in HH patients to assess AS and carotid-braquial PWV variation pre and post induced ischemia to assess ED. We compared these results against matching controls. PWV and PWV variation were assessed using Complior System (Artech-Medical, Francia). Carotid-femoral PWV was significantly increased in HH patients compared to control group (8.5 1.7 m/s vs 6.4 0.8 m/s, P