1,721,222 research outputs found
Non-alcoholic fatty liver disease: Diagnosis and investigation
No full textGiven the worldwide increase in obesity and diabetes, non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is associated with increased hepatic and extrahepatic morbidity and mortality, mainly related to non-alcoholic steatohepatitis with fibrosis. An early diagnosis in the high-risk population with features of insulin resistance and a proper identification of those patients with progressive liver disease are needed. Practicing physicians dealing with NAFLD should be aware of and should carefully evaluate the extended spectrum of NAFLD-related extrahepatic diseases, which significantly affects liver- and non-liver-related prognosis. This clinical practice-oriented article reviews the diagnostic methods and staging strategies for NAFLD and proposes an investigational algorithm for a global evaluation of NAFLD patients. © 2014 S. Karger AG, Basel
Recommendations for Management and Treatment of Nonalcoholic Steatohepatitis
No full textThe prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in conjunction with the epidemic increase in obesity and metabolic risk factors. Consequently, NAFLD has become a leading indication for liver transplantation. Although genetic factors play an important role in the pathogenesis of NAFLD, detrimental lifestyle trends favoring a calorically unrestricted diet rich in carbohydrates and unsaturated fat, prolonged sedentary periods or limited physical activity have major metabolic implications. In aggregate these physiological dysregulations constitute the main risk factors for the metabolic syndrome and NAFLD. The cornerstone of the treatment of NAFLD, is lifestyle changes, including modifications to diet and physical activity, to reduce body weight and liver fat, however adherence is notoriously poor and the epidemic of NAFLD continues to grow unimpeded. In the face of this unmet clinical need, the pharmacologic therapy of NAFLD has been expanding as the varied mechanistic pathways of NAFLD are elucidated. Beyond these approaches to treating NAFLD, the prevention of other liver diseases is additionally important. Chief among these is alcoholic liver disease, and heavy use is detrimental irrespective of underlying NAFLD. However, the impact of mild to moderate alcohol use in patients with mild or nonadvanced forms NAFLD is undefined. This article summarizes the results of the International Liver Transplantation Society consensus meeting on NAFLD in liver transplantation. It describes the available evidence and provides consensus guidance on the lifestyle and pharmacologic therapies of NAFLD, and the consensus position on alcohol use in patients with NAFLD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Role of chronic inflammation in advanced NAFLD : mechanisms, clinical impact and diagnostic strategies
No full textL’objectif général de ce travail était de mieux définir à travers des études cliniques le rôle de l’inflammation hépatique dans l’histoire naturelle de la NAFLD. La première étude a montré que les lésions d’inflammation lobulaire ou de fibrose, même minimes, sont associées avec un risque de progression de la maladie à moyen terme. Souvent cette progression s’accompagnait d’une aggravation des facteurs de risque métabolique. La deuxième étude a démontré que les facteurs de risque métaboliques sont fréquents chez les patients avec une maladie alcoolique du foie et augmentent significativement le risque de carcinome hépatocellulaire au stade de cirrhose. Ces résultats permettent d’identifier un groupe des patients buveurs excessifs ayant un risque élevé de carcinome hépatocellulaire. La troisième étude a porté sur une cohorte transversale de plus de 5000 patients. La stéatose était un facteur associé avec la présence des lésions d’athérosclérose indépendamment des facteurs de risque cardiovasculaire classiques. Dans une cohorte de 1800 patients suivis en moyenne 8 ans, nous avons montré que la stéatose était associée à la survenue des lésions d’athérosclérose carotidienne. Ces résultats, suggèrent que la stéatose est non seulement un marqueur de risque mais un facteur qui intervient dans la pathogenèse de l’athérosclérose carotidienne. En conclusion, nos résultats suggèrent que l'inflammation hépatique, dans un contexte de stéatose contribue à la progression des lésions hépatiques, favorise l'expression de médiateurs pro-athérogènes et l’activation des voies de carcinogenèse ce qui aurait pour effet l'apparition des complications extrahépatiques chez les patients avec NAFLD.The aim of this work was to analyze the role of chronic systemic inflammation into the natural history of NAFLD. We first undertook a study of NAFLD patients with repeat liver biopsies and demonstrated that mild lobular or portal inflammation or fibrosis in any location substantially increases the risk of progression to steatohepatitis or advanced fibrosis. Disease progression occurred concomitant with worsening of the metabolic conditions during follow-up. In the second study, we analyzed the prevalence and the impact of steatosis and metabolic risk factors on the risk of developing hepatocellular carcinoma in patients with alcoholic cirrhosis undergoing liver transplantation. The main finding of this study was that patients with advanced ALD have a high prevalence of NAFLD, and that this comorbid association confers a significantly increased risk of hepatocellular carcinoma. These findings are important for risk stratification of HCC in patients with ALD. In the third study we demonstrated that steatosis predicted carotid atherosclerosis independently of the association with classical cardiovascular risk factors. Second, in a subset of patients with longitudinal follow-up we demonstrated that baseline NAFLD was an independent predictor for incident carotid plaques. These results suggest that NAFLD is not only a marker but also an “active player” in the pathogenesis of atherosclerosis. In conclusion, our results suggests that low-grade chronic inflammation responsible for the production of pro-atherogenic cytokines and the activation of pro-oncogenic signaling pathways might be the link between liver fibrosis progression, hepatocellular carcinoma and cardiovascular risk
Development of a new diagnostic tool for sarcopenic obesity : associations with adipose tissue dysfunction, insulin resistance and severity of liver damage
No full textL'obésité sarcopénique (OS) est une condition caractérisée par la coexistence de l'obésité et de la sarcopénie, c'est-à-dire une réduction de la masse et de la fonction musculaires. Diagnostiquer l'OS est très complexe en raison de l'absence de critères diagnostiques universellement acceptés, ce qui entraîne des diagnostics imprécis et une estimation hautement variable de sa prévalence. Face à ces limitations, l'objectif de cette thèse était de développer un outil de diagnostic empirique pour l'OS aidé d'intelligence artificielle, basé sur l'analyse de la composition corporelle. Nous avons élaboré l'AIM-SO score dans une population de sujets en surpoids/obésité puis nous l'avons testé dans deux autres populations, l'une de patients avec obésité sévère subissant une chirurgie bariatrique, l'autre dans la population générale de l'UK Biobank. Une étude longitudinale a également été menée, avec un suivi à un an chez les sujets ayant subi une chirurgie bariatrique. Nous avons étudié les corrélations cliniques, en particulier cardiométaboliques et hépatiques, notamment histologiques per-opératoires, dans la cohorte bariatrique. La prévalence d'OS a été très proche entre ces trois cohortes. L'OS diagnostiquée par l'AIM-SO score était associée à de multiples comorbidités cardiométaboliques, ainsi qu'à une forme plus sévère d'atteinte inflammatoire et fibrosante du foie. Malgré la perte de poids, le bénéfice métabolique (rémission des comorbidités) après chirurgie bariatrique était moindre chez les patients ayant une OS. Des analyses préliminaires de la cohorte UK Biobank ont montré une association significative entre l'OS diagnostiquée par l'AIM-SO score et des paramètres de fonctionnalité musculaire, en particulier la force musculaire. Nous proposons ce nouvel outil diagnostique pour standardiser le diagnostic d'OS et identifier des patients en situation d'obésité avec sarcopénie dont le phénotype cardiométabolique et hépatique est plus sévère. Le diagnostic d'OS pourrait également renseigner le bénéfice attendu des différentes interventions à visée de réduction pondérale participant ainsi à une prise en charge médicale personnalisée.Sarcopenic obesity (SO) is a condition characterized by the coexistence of obesity and sarcopenia, the latter defined as a reduction in muscle mass and function. Diagnosing SO is highly complex due to the lack of universally accepted diagnostic criteria, leading to imprecise diagnoses and highly variable prevalence estimates. Given this scenario, this thesis aimed to develop an empirical diagnostic tool for SO using artificial intelligence, based on the analysis of body composition. We developed the AIM-SO score in a population of patients with overweight/obesity and tested it in two other populations: patients with severe obesity undergoing bariatric surgery (BS) and the general population of the UK Biobank. A longitudinal study with a one-year follow-up was conducted in subjects who underwent BS. We examined clinical correlations, particularly cardiometabolic and hepatic, including perioperative histological findings in the bariatric cohort. The prevalence of SO was similar across these three cohorts. SO diagnosed by the AIM-SO score was associated with multiple cardiometabolic comorbidities and more severe inflammatory and fibrosing liver damage. Despite weight loss, the metabolic benefit (remission of comorbidities) after BS was lower in patients with SO. Preliminary analyses of the UK Biobank cohort showed a significant association between SO diagnosed by the AIM-SO score and parameters of muscular functionality, particularly muscle strength. We propose this new diagnostic tool to standardize the SO diagnosis and identify patients with obesity and sarcopenia who exhibit more severe cardiometabolic and hepatic phenotype. Diagnosing SO could also inform the expected benefit of various weight loss interventions, thus contributing to personalized medical management
Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease
Full text linkBackground: Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion. Aim: We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF). Methods: We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2-4 Kleiner's stages. Results: 84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60% vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57% vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022). Conclusions: Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high-risk population
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