Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation

We evaluated whether the lack of TNF-α signaling increases mucosal levels of annexin A1 (AnxA1); the hypothesis stems from previous findings showing that TNF-α neutralization in Crohn´s disease patients up-regulates systemic AnxA1 expression. Biopsies from healthy volunteers and patients under anti-TNF-α therapy with remittent ulcerative colitis (UC) showed higher AnxA1 expression than those with active disease. We also evaluated dextran sulfate sodium (DSS)-acute colitis in TNF-α receptor 1 KO (TNFR1-/-) strain with impaired TNF-α signaling and C57BL/6 (WT) mice. Although both strains developed colitis, TNFR1-/- mice showed early clinical recovery, lower myeloperoxidase (MPO) activity and milder histopathological alterations. Colonic epithelium from control and DSS-treated TNFR1-/- mice showed intense AnxA1 expression and AnxA1+ CD4+ and CD8+ T cells were more frequent in TNFR1-/- animals, suggesting an extra supply of AnxA1. The pan antagonist of AnxA1 receptors exacerbated the colitis outcome in TNFR1-/- mice, supporting the pivotal role of AnxA1 in the early recovery. Our findings demonstrate that the TNF-α signaling reduction favors the expression and biological activity of AnxA1 in inflamed intestinal mucosa.Fil: Sena, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pedrotti, Luciano Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Barrios, Bibiana Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cejas, Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Balderramo, Domingo. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Diller, Ana. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort

Background: The rs641738 C &gt; T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population. Aims: We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans. Methods: Patients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression. Results:In total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66–2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59–2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10–6.87, p = 0.031). Conclusion: The rs631738 C &gt; T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD. Graphical Abstract: [Figure not available: see fulltext.]</p

Assessment of <i>TLL1 </i>variant and risk of hepatocellular carcinoma in Latin Americans and Europeans

Introduction and Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. Materials and Methods: Cross-sectional analysis performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). Results: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). Conclusions: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC development in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.</p

Hepatitis E virus infection in pregnant women, Argentina

Background: Hepatitis E virus (HEV) infection is an important cause of acute hepatitis worldwide. In pregnant women, HEV can cause more severe symptoms, with high rates of fatal hepatic failure in endemic countries. However, HEV prevalence and circulation among pregnant women from South America is almost unknown. We aimed to investigate HEV infection in pregnant women for the first time in Argentina. Methods: IgG and IgM anti-HEV antibodies and RNA-HEV were investigated (by ELISA assays and RT-Nested-PCR, respectively) in 202 serum samples from pregnant women collected in the central region of Argentina between 2015 and 2017. A control group of 155 non-pregnant women was included (year 2018). Results: The IgG anti-HEV positivity rate was 8.4% (17/202), higher than the 2.6% (4/155) obtained for the non-pregnant women control group, and showing association between pregnancy and HEV infection (p = 0.023, OR = 3.5, CI95% = 1.1-10.5). Women younger than 25 years old presented higher levels of antibodies, and there were no differences in the prevalences between trimesters of pregnancy. Two samples were reactive for IgM anti-HEV, showing recent infections, although no symptoms were registered in these patients. All samples were negative for RNA-HEV amplification. Conclusions: HEV produces infections in pregnant women from Argentina, alerting health teams to consider it as a possible cause of liver disease.Fil: Tissera, Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lardizabal, María Cecilia. Hospital Privado Universitario de Córdoba; ArgentinaFil: Torres, Sofía Belén. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Fantilli, Anabella Clara. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Martínez Wassaf, Maribel G.. Laboratorio de Análisis Clínicos Especializados; ArgentinaFil: Venezuela, Raul Fernando. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Capra, Raul Horacio. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Balderramo, Domingo. Hospital Privado Centro Médico de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Travella, Claudia. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pisano, María Belén. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Características de las infecciones del torrente sanguíneo en pacientes adultos de dos centros de tercer nivel de Córdoba, Argentina

Introducción: Las infecciones del torrente sanguíneo (ITS) generan elevada morbimortalidad. Objetivo: Determinar características epidemiológicas, microbiológicas y clínicas de ITS adquiridas en la comunidad (ITS-AC) e intrahospitalarias (ITS-IH). Métodos: Se analizaron retrospectivamente eventos de bacteriemia y fungemia en dos hospitales de tercer nivel entre abril de 2009 y agosto de 2013.  Resultados: Se identificaron 1150 eventos de ITS, 53% ITS-AC. El 61% de microorganismos aislados fueron gram negativos. Los patógenos más frecuentes fueron Escherichia coli en ITS-AC y Klebsiella pneumoniae en ITS-IH.  Staphylococcus aureus fue el gram positivo más frecuente. Las principales comorbilidades fueron enfermedad renal (39%) y neoplasias (38%). El 26,8% de ITS fueron primarias. Los focos infecciosos más frecuentes fueron respiratorio (17%) y urinario (16,9%). Un elevado porcentaje de gram negativos en ITS-AC e ITS-IH fueron resistentes a ampicilina sulbactam (40,2% y 57,5%), cefalotina (36,7% y 46,8%), trimetoprima-sulfametoxazol (32,8% vs 35,5%) y ciprofloxacina (24,6% y 35,3%). Staphylococcus aureus meticilino resistente fue más frecuente en ITS-IH (31,4% vs 11,8%, p=0,007). Conclusiones: Las características clínicas y epidemiológicas de ITS fueron similares a las reportadas por otros estudios latinoamericanos. Pero observamos algunas diferencias en los perfiles de susceptibilidad antimicrobiana. Resaltamos la importancia de la vigilancia epidemiológica local para elegir tratamientos empíricos apropiados.</p

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

EDITORIAL Management of biliary complications after orthotopic liver transplantation: The role of endoscopy

Biliary complications are significant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%, however, these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde cholangiography (ERC). Other complications such as bile duct stones, bile casts, sphincter of Oddi dysfunction, and hemobilia, are less frequent and also can be managed with ERC. This article will review the risk factors, diagnosis, and endoscopic management of the most common biliary complications after OLT

Management of biliary complications after orthotopic liver transplantation: The role of endoscopy

Biliary complications are significant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%, however, these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde cholangiography (ERC). Other complications such as bile duct stones, bile casts, sphincter of Oddi dysfunction, and hemobilia, are less frequent and also can be managed with ERC. This article will review the risk factors, diagnosis, and endoscopic management of the most common biliary complications after OLT

Subcapsular liver hematoma after endoscopic retrograde cholangiopancreatography in a liver transplant recipient

Endoscopic Retrograde Cholangiopancreatography (ERCP) is commonly performed in patients after liver transplantation. The most common indications for ERCP include treatment of bile leaks and anastomotic and nonanastomotic biliary strictures. In this report we describe an unusual complication of ERCP in a liver transplant recipient with a bile leak two months after orthotopic liver transplantation (OLT). After confirming a bile leak, a hydrophilic guide wire was placed in the intrahepatic duct, an endoscopic sphincterotomy was performed, and a biliary plastic stent was successfully placed over the wire across the bile leak. Within the following 24 hours the patient developed a sharp right-sided upper quadrant pain and a drop in his hemoglobin level. An abdominal CT scan demonstrated a subcapsular hepatic hematoma that was successfully managed conservatively