Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

Background and Aim: Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). Methods: Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years). Results: Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). M ore t han 7 0% o f n on-NASH p atients s howed s ome i nflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these. Conclusions: The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death

Role of the rs10401670 variant in the resistin gene on the metabolic response after weight loss secondary to a high‐fat hypocaloric diet with a Mediterranean pattern

Producción CientíficaBackground:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet

Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology

Hepatic fibrosis; Non-alcoholic steatohepatitis; Transient elastographyFibrosis hepática; Esteatohepatitis no alcohólica; Elastografía transitoriaFibrosi hepàtica; Esteatohepatitis no alcohòlica; Elastografia transitòriaBackground & Aims Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. Results From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13–8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29–5.98) and 0.70% (95% CI 0.10–4.95) respectively. Conclusions These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available

Bacterial antigen translocation and age as BMI-independent contributing factors on systemic inflammation in NAFLD patients

Background & Aims Low‐grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients. Patients & Methods Multicenter cross‐sectional study including consecutive patients with biopsy‐proven NAFLD. Demographic, metabolic and fibrosis‐related variables were collected. Circulating bacterial antigens were quantified in blood. Toll‐like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro. Results Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI 30 (77.3%) (P = .014). HOMA‐IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non‐obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro‐inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF‐α and IL‐6, in both BMI subgroups of patients. Age independently influenced TNF‐α and IL‐6 in non‐obese patients, and TNF‐α in obese patients. Conclusion Serum circulating bacterial antigens as well as age were BMI‐independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients.This work has been funded by grants PI16/0967 and PI17/0535 from Instituto de Salud Carlos III, Madrid, Spain, and PROMETEO 2016/001 from Generalitat Valenciana, Valencia, Spain. IGH was recipient of a Young Investigator Grant by CIBERehd, Instituto de Salud Carlos III, Madrid, Spain

Estar en las redes: Estrategias de visibilización e interacción desde una cuenta de comunicación científica (Entramando Saberes, FFYL, UBA)

Entramando Saberes es un Programa de Extensión de la Facultad de Filosofía y Letras (UBA) compuesto por graduades y estudiantes de las carreras de Antropología, Arqueología e Historia. Desde fines de 2016, nos embarcamos en un proyecto para entablar diálogos con un público amplio, por fuera del ámbito académico, con el cual compartir los conocimientos de nuestras disciplinas a través de distintas herramientas de comunicación. En este artículo reconstruimos nuestra trayectoria como equipo y los desafíos que se nos presentaron al ‘estar en las redes’, específicamente en las plataformas digitales de Facebook e Instagram. Discutimos las estrategias para generar contenidos que, sin perder la rigurosidad, sean atractivos, llamen a la reflexión y construyan lazos con la comunidad no académica. Asimismo, consideramos el impacto que la coyuntura de pandemia tuvo en nuestras prácticas. Para finalizar, reflexionamos sobre el trabajo colectivo y el enfoque de comunicación del equipo.Entramando Saberes is an Extension Program in Facultad de Filosofía y Letras (UBA). It is formed by graduates and students of Anthropology, Archaeology and History. Since 2017, we have taken on the challenge of establishing dialogues with a broad audience outside of the academic field, with whom we share our disciplines’ knowledge through various communication tools. In this paper, we describe our trajectory as a team, and the issues we had to tackle when ‘being online’, specifically on the digital platforms of Facebook and Instagram. We discuss strategies to create content that needs to be appealing while remaining accurate, to encourage reflection and to help build bonds with the non-academic community. Furthermore, we consider the impact that the pandemic has had on our practices. Lastly, we reflect on collective work and the team’s communicational approach.Fil: Aller, Roberta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas; ArgentinaFil: Ortiz, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Sociales. Instituto de Desarrollo Económico y Social. Centro de Investigaciones Sociales; ArgentinaFil: García, Marisol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; ArgentinaFil: Gómez Vázquez, Lucila. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Santarcieri, Rocío. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Ramos, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas; ArgentinaFil: Costilla, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas; Argentin

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors

Spanish Neuroendocrine Tumor Group (GETNE)© 2015, Springer Science+Business Media New York. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients’ well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.This project was funded in part by a restricted educational grant from Novartis Spain and by support from the Spanish Neuroendocrine Tumor Group (GETNE).Peer Reviewe

Obesidad en España y Castilla y León: ¿qué nos dicen los estudios?

La obesidad, es la epidemia del siglo XXI, se define como un peso corporal desproporcionado para la altura con una acumulación excesiva de tejido adiposo que se acompaña habitualmente de una inflamación sistémica crónica leve. Para clasificar a los pacientes con obesidad se utiliza el índice de Quetelet o índice de masa corporal, que se obtiene dividiendo el peso del individuo en Kg entre la talla al cuadrado en metros (kg/m2). Un índice de masa corporal por encima de 30 kg/m2 se considera como obesidad. La obesidad está asociada con el desarrollo de diabetes mellitus tipo 2, enfermedades cardiovasculares, algunos tipos de cáncer y otras condiciones patológicas crónicas. La circunferencia de la cintura también es un marcador de riesgo, en obesidad. En el estudio ENPE, se demostró una prevalencia en la población española de sobrepeso de 39,3% y de obesidad de 21,6%. La prevalencia de sobrepeso en mujeres fue de 32,1% y de obesidad de 22,8%, en varones, por otra parte, la obesidad represento un 20,5% y el sobrepeso un 46,5 %. Recientemente, en Castilla y León, la Consejería de Sanidad ha publicado los resultados de un estudio de cohortes “Estudio de Riesgo Cardiovascular en Castilla y León; la evolución de los Factores de Riesgo cardiovascular 2004-2014”. La prevalencia de obesidad (IMC ≥30) en 2004 era en nuestra Comunidad Autónoma de 22,9%. En la reevaluación de la misma cohorte de pacientes, diez años más tarde, esa proporción ha aumentado hasta el 27,6%, casi 5 puntos porcentuales. Con respecto al total de la muestra de 2014, el 31,1% tenían normopeso, el 41,3% tenían sobrepeso y el 26,1% tenían un IMC entre 30 y 40 (obesidad) y un 1,6% presentaban un IMC>40.En conclusión, la obesidad se ha convertido en una pandemia a nivel mundial, situándose España en una zona intermedia de prevalencia, así como Castilla y León. EL índice de masa corporal, así como la circunferencia de la cintura son las herramientas más utilizadas a la hora de realizar los estudios de prevalencia de obesidad.Obesity, the epidemic of the 21st century (1), is defined as a disproportionate body weight for height with an excessive accumulation of adipose tissue that is usually accompanied by a mild chronic systemic inflammation. To classify patients with obesity, the Quetelet index or body mass index is used, which is obtained by dividing the weight of the individual in Kg by the square height in meters (kg/m2). A body mass index above 30 kg/m2 is considered as obesity. Obesity is associated with the development of type 2 diabetes mellitus, cardiovascular diseases, some types of cancer and other chronic pathological conditions. Waist circumference is a risk factor in obesity, too. In the ENPE study, a prevalence in the Spanish population of overweight of 39.3% and of obesity of 21.6% was demonstrated. The prevalence of overweight in women was 32.1% and obesity 22.8%, in men; on the other hand, obesity represented 20.5% and overweight 46.5%. Recently, Castilla y León Health System has published the results of a study of cohorts “Cardiovascular Risk Study in Castilla y León; the evolution of cardiovascular risk factors 2004-2014 “. The prevalence of obesity (BMI ≥30) in 2004 was 22.9% in our Autonomous Community. In the re-evaluation of the same cohort of patients, ten years later, that proportion has increased to 27.6%, almost 5 percentage points. With respect to the total sample of 2014, 31.1% had normal weight, 41.3% were overweight and 26.1% had a BMI between 30 and 40 (obesity) and a 1, 6% had a BMI> 40 In conclusion, obesity has become a pandemic worldwide, placing Spain in an intermediate zone of prevalence as well as Castilla y León. The body mass index, as well as the circumference of the waist are the most used tools when carrying out obesity prevalence studie

Relation of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naı¨ve diabetes obese patients

Producción CientíficaBackground: The aim of the present study was to explore the relationship of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naı¨ve diabetic patients. Subjects: A population of 66 naı¨ve diabetic patients with obesity was analyzed. A complete nutritional and biochemical evaluation was performed. Results: The mean age 56.9 11.6 years and the mean BMI was 37.8 6.3. Patients were divided in two groups by median resistin value (3.3 ng/ml), group I (patients with the low values, average value 2.5 0.5) and group II (patients with the high values, average value 4.8 1.8). Patients in the group I had lower waist circumference, total cholesterol, LDLcholesterol and C-reactive protein than patients in group II. Correlation analysis showed a significant correlation among resistin levels and the independent variables; BMI (r = 0.26; p < 0.05), waist circumference (r = 0.38; p < 0.05), fat mass (r = 0.28; p < 0.05), LDL-cholesterol (r = 0.3; p < 0.05), C-reactive protein (r = 0.28; p < 0.05). In the multivariate analysis, resistin concentration increase 0.024 ng/ml (CI 95%: 0.006–0.42) for each mg/dl of C-reactive protein. Conclusion: Circulating resistins are associated with C-reactive protein in an independent way in naı¨ve diabetic patients

Role of Oxidative Stress and Lipid Peroxidation in the Pathophysiology of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is characterised by an excess of hepatic fat that can progress to steatohepatitis, fibrosis, cirrhosis and hepatocarcinoma. The imbalance between lipid uptake/lipogenesis and lipid oxidation/secretion in the liver is a major feature of NAFLD. Given the lack of a non-invasive and reliable methods for the diagnosis of non-alcoholic steatohepatitis (NASH), it is important to find serum markers that are capable of discriminating or defining patients with this stage of NASH. Blood samples were obtained from 152 Caucasian subjects with biopsy-proven NAFLD due to persistently elevated liver enzyme levels. Metabolites representative of oxidative stress were assessed. The findings derived from this work revealed that NAFLD patients with a NASH score of ≥ 4 showed significantly higher levels of lipid peroxidation (LPO). Indeed, LPO levels above the optimal operating point (OOP) of 315.39 μM are an independent risk factor for presenting a NASH score of ≥ 4 (OR: 4.71; 95% CI: 1.68–13.19; p = 0.003). The area under the curve (AUC = 0.81, 95% CI = 0.73–0.89, p < 0.001) shows a good discrimination ability of the model. Therefore, understanding the molecular mechanisms underlying the basal inflammation present in these patients is postulated as a possible source of biomarkers and therapeutic targets in NASH.This research was funded by Consejería de Educación de Castilla y León (VA256P20), Instituto de Salud Carlos III (Grant CB21/13/0005, PI21/00917 and COV20/00491), Junta de Castilla y León (18IGOF), Gerencia Regional de Salud de Castilla y León (GRS2398/A/21), Fundación Ramón Areces (CIVP19A5953) and 7th Call for Gilead Biomedical Research Grants in HIV, Liver Diseases and Haemato-oncology

Accuracy of urea breath test performed immediately after emergency endoscopy in peptic ulcer bleeding

Producción CientíficaThe aim of this work is to investigate the accuracy of the urea breath test (UBT) performed immediately after emergency endoscopy in peptic ulcer bleeding (PUB). METHODS: Urea breath test was carried out right after emergency endoscopy in patients with PUB. The accuracy of this early UBT was compared to a delayed one after hospital discharge that was considered the gold standard. Clinical and epidemiological factors were analyzed in order to study their influence on the accuracy of the early UBT. RESULTS: Early UBT was collected without any complication and good acceptance from all the 74 patients included. In 53 of the patients (71.6%), a delayed UBT was obtained. Comparing concordance between the two tests we have calculated an accuracy of 83% for the early UBT. Sensibility and specificity were 86.36 and 66%, respectively, with a positive predictive value of 92.68% and negative predictive value of 50% (Kappa index = 0.468; p = 0.0005; CI: 95%). We found no influence of epidemiological factors, clinical presentation, drugs, times to gastroscopy, Forrest classification, endoscopic therapy, hemoglobin, and urea levels over the accuracy of early UBT. CONCLUSIONS: Urea breath test carried out right after emergency endoscopy in PUB is an effective, safe, and easy-to-perform procedure. The accuracy of the test is not modified by clinical or epidemiological factors, ulcer stage, or by the type of therapy applied. However, we have found a low negative predictive value for early UBT, so a delayed test is mandatory for all negative cases