Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.Fil: Bessone, Fernando. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Hospital Nacional del Centenario; ArgentinaFil: Poles, Natalia. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Hospital Nacional del Centenario; ArgentinaFil: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentin

Presence and characterization of Escherichia coli virulence genes isolated from diseased pigs in the central region of Argentina

Background: The main pathogen of neonatal and post weaning diarrhea and edema disease (ED) is Escherichia coli and pathotypes involved are enterotoxigenic, enteropathogenic, and shiga toxigenic (ETEC, EPEC, and STEC, respectively). Those diseases cause economic loss in pig production. Aim: The aim of this work was to evaluate the presence of strains expressing virulence markers genes and the antibiotic susceptibility profiles of E. coli from clinical cases of post weaning diarrhea and ED in farms in the central area of Argentina. Materials and Methods: Intensive pig farms from the central region of Argentina were sampled. Intestinal mucosa swabs from pigs with diarrhea were taken, seeded on MacConkey agar plates, biochemically typified and tested by polymerase chain reaction (PCR). Antibiograms were made by disk-diffusion method. Results: A total of 54 strains from clinical cases studied showed PCR findings: 88.88% (48/54) expressed at least one gene coding for a virulence factor. Colonization factors found were: 39.58% of strains had F18, 33.33% were F4 and 31.25% adhesin involved in diffuse adherence-I; 29.17%, 25%, and 2.1% expressed LT, STb, and STa, respectively. 25% were STx and 16.67% were eae positive. Only 2.1% were STx2. The most active antibiotics against most strains were gentamicin and ceftiofur, but resistance profiles against many antibiotics were found. Conclusion: High circulation of pathogens strains of E. coli among pigs with diarrhea with an extended antibiotic resistance profile.EEA Marcos JuárezFil: Bessone, Fernando Aní­bal. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Bessone, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Marini, Sebastián José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Conde, María Belén. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Alustiza, Fabrisio Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Zielinski, Gustavo Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; Argentin

Assessment of an Aujeszky’s disease control strategy in a highly prevalent pig farm based on systematic vaccination with an inactivated gE-negative marker vaccine

Aujeszky's disease (AD) is endemic in Argentina. In 2016, an inactivated gE- negative marker Bartha K61 vaccine (AUSKIPRA® BK) was launched for use, making Argentina the only country to carry out a control strategy plan with it. In the present article, we describe the results of a control program in a farrow-to-finishing farm with high initial AD prevalence (33% in sows), based on the systematic vaccination, detection, and elimination of seropositive pigs, the replacement of sows with vaccinated gilts, and the instauration of artificial insemination. The program was suitable for diminishing the incidence and the prevalence at levels consistent with virus eradication. This situation has been sustained over time. This is the first report of AUSKIPRA® BK efficacy under field conditions.Instituto de PatobiologíaFil: Aznar, Maria Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Bessone, Fernando Aní­bal. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Segurado, Rodrigo. Veterinario privado; ArgentinaFil: Duffy, Sergio. Consultor privado; Argentin

Checkpoint inhibitor-induced hepatotoxicity : Role of liver biopsy and management approach

©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.Immunological checkpoint inhibitors (ICIs) have revolutionized therapy of many different malignanices. Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin, lungs, gastrointestinal and endocrine organs as well as the liver. Liver injury has been reported in 3%-8% of patients with grade III-IV hepatitis in retrospective studies. The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation. The role for liver biopsy (LB) in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management. LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected. Although there are no distinctive histological features, the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs. The natural history of hepatotoxicity of ICI therapy is not well known. Recent studies have demonstrated that 33%-50% of patients improve spontaneously with discontinuation of ICIs. In patients with jaundice and/or coagulopathy corticosteroids are used. The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial. Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens. Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.Peer reviewe

The Tumor Microenvironment as a Regulator of Endocrine Resistance in Breast Cancer

Estrogen receptor positive breast neoplasias represent over 70% of diagnosed breast cancers. Depending on the stage at which the tumor is detected, HER2 status and genomic risk, endocrine therapy is combined with either radio, chemo and/or targeted therapy. A growing amount of evidence supports the notion that components of the tumor microenvironment play specific roles in response to treatment and that strategies targeting these key interactions with tumor cells could pave the way to a new generation of therapies. In this review, we analyze the evidence suggesting different components of the tumor microenvironment play a role in hormone receptor positive breast cancer progression. In particular we focus on the immune system, carcinoma associated fibroblasts and the extracellular matrix. Further insight into the cross talk between these constituents of the microenvironment and the tumor cells may lead to therapies that eliminate disseminated metastatic cells early on, and thus reduce distant disease relapse which is the leading cause of death for patients who are diagnosed with this illness.Fil: Díaz Bessone, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Gattás, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Laporte, Fernando Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Tanaka, Max. Vrije Universiteit Amsterdam; Países Bajos. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

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

Characterization and comparison of strains of Pasteurella multocida associated with cases of progressive atrophic rhinitis and porcine pneumonia in Argentina

Pasteurella multocida (Pm) is the causative agent of progressive atrophic rhinitis (PAR) and pneumonicpasteurellosis (PN) in pigs. Pm is a member of the porcine respiratory complex responsible for important economic loss inthe pig industry. This study aimed to characterize the Pm strains recovered from clinical cases of PN and PAR and to elucidate theantibiotic susceptibility profiles of the strains.Materials and Methods: Sixty strains were characterized molecularly by polymerase chain reaction to determine speciesspecific gene, capsular type (A or D), and toxin A production. The agar diffusion method was employed to evaluate antibioticresistance profiles. We found that 65% of strains belonged to capsular type A or D, and 15% of those were positive to toxA gene.The antibiotic susceptibility profiles found were sensitive in decreasing order to: Enrofloxacin, ceftiofur (CTF), ampicillin,tilmicosin (TIL), florfenicol (FFN), spectinomycin (SPC), gentamicin, oxytetracycline (OTC), and trimethoprimsulfamethoxazole (TMS). Strains were resistant in decreasing order to: Lincomycin (LIN), tylosin (TYL), erythromycin(ERY), TMS, SPC, OTC, FFN, TIL, and CTF. The toxA gene was detected in many Pm isolates from pneumonic lungs. Capsule type A or D was the mostfrequently found among the collected isolates. LIN, TYL, and ERY are the drugs which showed higher percentages of resistant isolates.Fil: Bessone, Fernando Anibal. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Soriano Pérez, María Laura. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zielinski, Gustavo Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Dibárbora, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Conde, María Belén. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Cappuccio, Javier Alejandro. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alustiza, Fabrisio Eduardo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.Fil: Bessone, Fernando. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Hospital Nacional del Centenario; ArgentinaFil: Hernandez, Nelia. Hospital de Clinicas Dr. Manuel Quintela; UruguayFil: Tagle, Martin. Universidad Peruana Cayetano Heredia; PerúFil: Arrese, Marco. Pontificia Universidad Católica de Chile; ChileFil: Parana, Raymundo. Universidade Federal da Bahia; BrasilFil: Mendez-Sánchez, Nahum. Fundacion Clinica Medica Sur; México. Universidad Nacional Autónoma de México; MéxicoFil: 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: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Dagher, Lucy. Policlinica Metropolitana; VenezuelaFil: Contreras, Fernando. Universidad Pedro Henriquez Urena; República DominicanaFil: Fassio, Eduardo. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Pesoa, Mario. Hospital de Clincas; BrasilFil: Brahm, Javier. Clinica Las Condes; ChileFil: Silva, Marcelo. Universidad Austral. Hospital Universitario Austral; Argentin

High Prevalence of Hepatitis C Virus Genotype 1b Infection in a Small Town of Argentina. Phylogenetic and Bayesian Coalescent Analysis

Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina)

The role of viral particle integrity in the serological assessment of foot-and-mouth disease virus vaccine-induced immunity in swine

The efficacy of foot-and-mouth disease virus (FMDV) inactivated vaccines is mainly dependent on the integrity of the whole (146S) viral particles. If the intact capsids disassemble to 12S subunits, antibodies against internal-not protective epitopes, may be induced. Serological correlates with protection may be hampered if antibodies against internal epitopes are measured. Here we compared the performance of different ELISAs with the virus-neutralization test (VNT) that measures antibodies against exposed epitopes. Sera from pigs immunized with one dose of an expired commercial FMDV vaccine were used. This vaccine contained about 50% of O1/Campos and over 90% of A24/Cruzeiro strains total antigen as whole 146S particles. Specific-total antibodies were measured with the standard liquid-phase blocking ELISA (LPBE). We also developed an indirect ELISA (IE) using sucrose gradient purified 146S particles as capture antigen to titrate total antibodies, IgM, IgG1 and IgG2. A good correlation was found between VNT titers and IgG-ELISAs for A24/Cruzeiro, with the lowest correlation coefficient estimated for IgG2 titers. For O1/Campos, however, the presence of antibodies against epitopes different from those of the whole capsid, elicited by the presence of 12S particles in the vaccine, hampered the correlation between LPBE and VNT, which was improved by using purified O1/Campos 146S-particles for the liquid-phase of the LPBE. Interestingly, 146S particles but not 12S were efficiently bound to the ELISA plates, confirming the efficiency of the IE to detect antibodies against exposed epitopes. Our results indicate that any serological test assessing total antibodies or IgG1 against epitopes exposed in intact 146S-particles correlate with the levels of serum neutralizing antibodies in vaccinated pigs, and might potentially replace the VNT, upon validation. We recommend that antigen used for serological assays aimed to measure protective antibodies against FMDV should be controlled to ensure the preservation of 146S viral particles.Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Turco, Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Miraglia, Maria Cruz. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Bessone, Fernando Anibal. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Franco, Raúl. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Pérez Filgueira, Daniel Mariano. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Sala, Juan Manuel. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentin