1,721,242 research outputs found
From nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD): more than a single-letter change in an acronym. Commentary
No full textNonalcoholic fatty liver disease (NAFLD) is an increasingly recognized public health problem worldwide. To emphasize the close pathophysiological links between NAFLD and overweight/obesity, insulin resistance, and related metabolic comorbidities, a consensus statement of international experts in 2020 has recommended to replace the old acronym NAFLD with “metabolic dysfunction-associated fatty liver disease” (MAFLD). A set of “positive” criteria to diagnose MAFLD, regardless of daily alcohol consumption, has also been proposed. A “positive” definition of MAFLD and its special focus on the metabolic causative drivers of this liver disease is expected to reduce patient confusion on disease etiology, which can, in turn, improve the identification and awareness of this common and burdensome liver disease among both primary care physicians and specialists. However, the proposal to change the terminology from NAFLD to MAFLD is still under intense discussion, as also recently highlighted by a panel of international experts (led by Dr. Polyzos and Mantzoros), which is the main topic of discussion of this commentary. Further studies are required to better understand whether, and how, the proposed changes to the diagnostic criteria for MAFLD may impact on the risk of adverse hepatic and extra-hepatic clinical outcomes
NAFLD in the 20’s. From Epidemiology to Management (PART - II). Editorial
No full textThis second part of the single-topic issue entitled “NAFLD in the 20’s. From epidemiology to management” concludes this special issue of CPD. Nonalcoholic fatty liver disease (NAFLD) is an “umbrella” definition, which describes the whole range of pathological liver changes spanning from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH may be associated with fibrosis, which carries an increased risk of progressing to either cirrhosis or hepatocellular carcinoma (HCC), which, in this case, is defined as NAFLD-related HCC. Given that NAFLD affects up to a quarter of the general adult population in Europe and USA and owing to the global decline of other causes of chronic liver disease, such as viral hepatitis, NAFLD is rapidly becoming the leading cause of HCC worldwide. In addition to its liver-related burden, NAFLD is also associated with an increased risk of adverse cardiovascular events and other extra-hepatic diseases. Therefore, the prediction of the natural history of this common and burdensome liver disease is key in implementing personalized management and follow-up strategies. On this background, Tovoli et al. from the group led by Professor Piscaglia in Bologna, Italy, have examined published studies pertinent to characterizing those features of NAFLD-related HCC useful in distinguishing this specific etiology of HCC from cases of HCC owing to other non-NAFLD etiologies in humans [1]. In their systematic review, these authors were able to retrieve a total of 244 eligible original papers. Data have shown that NAFLD-related HCC may often escape the surveillance programs given that it is difficult to precisely identify the population at high-risk, and that NAFLD-related HCC may also occur amongst patients with non-cirrhotic NASH. These specific features will result in delayed diagnoses, more limited access to radical management options and, eventually, in a reduced life expectancy which is not due to inherently more aggressive behavior of HCC. On these grounds, it is expected that additional efforts to further improve prevention, surveillance protocols and identification of drugs modifying the course of NAFLD will beneficially impact healthcare expenditures and clinical outcomes of patients with NAFLD-related HCC [1]. Dr. Ballestri et al. from Modena, Italy, have highlighted the importance of diagnosing NAFLD through non-invasive imaging techniques [2]. In their extensive review of the literature, the authors examined the added value of conventional liver ultrasonography when performed with semi-quantitative scores. These simple ultrasonographic scores can effectively rate the severity of steatosis and its progression over time (indicating those subjects, who should undergo second-line imaging techniques or liver biopsy), while also acting as accurate sensors of cardio- metabolic health [2]. Along the same line, Dr Pennisi et al. from the group led by Prof. Petta, Palermo, Italy, have extensively discussed the main limitations of liver biopsy for the diagnosis of NAFLD. These include the invasiveness and potentially life-threatening, albeit rare complications of this method, as well as its poor acceptability, sampling variability and costs [3]. On these grounds, the authors have critically discussed the clinical importance of differentiating simple steatosis from NASH as well as of non-invasively assessing liver fibrosis [3]. We are grateful to the CPD Editorial Team for granting us the honor to serve as Guest Editors of this single-topic issue. We also thank all those Colleagues who accepted to contribute their outstanding articles to the present monography to which we wish great success
Genetic and biochemical heterogeneity of cardiac troponins: clinical and laboratory implications.
No full textThe contractile sarcomeric pool of skeletal muscle and heart consists of a highly-ordered arrangement of actin thin filaments, tropomyosin and proteins of the troponin complex: troponin I (TnI), troponin T (TnT) and troponin C (TnC). The cardiac myocyte expresses specific isoforms of both TnI and TnT (cTnI and cTnT, respectively), which can be distinguished from skeletal muscle isoforms by rapid and reliable immunoassays. Due to their superior cardiac specificity, cTnI and cTnT have become the recommended biomarkers for the diagnosis of myocardial injury. The most common applications are for risk stratification and diagnosis of acute coronary syndromes, albeit they can also be used for assessing a variety of other myocardial disorders. However, the excellent diagnostic efficiency of cardiac troponin testing is jeopardized by some pre-analytical issues (unsuitable specimens for testing, analyte stability, handling, transportation and storage of specimens prior to analysis), as well as by analytical concerns related to standardization or harmonization of cTnI immunoassays, imprecision at low concentrations, antibody specificity, immunoreactivity of plasma isoforms released in the blood after myocardial injury, interference from autoantibodies, heterophilic antibodies, rheumatoid factor, and human anti-mouse antibodies. In addition, although the influence of some known mutations in cTnT and cTnI on calcium sensitivity and force generation have been readily demonstrated, their influence on current immunoassays is unknown. Most mutations in these proteins may contribute to the development of certain cardiomyopathies, namely hypertrophic and restrictive. In these situations, the phenotype is characterized by the underlying diseases, and the ability to detect cTnT or cTnI is of relatively little clinical significance. However, the cTnT Arg129Lys polymorphism and those observed in the stable domain of cTnI do not significantly alter the functional properties of the molecule within the myocardium and thus are predictably asymptomatic. While the actual prevalence of these polymorphisms in the general population is still unknown, they might be a source of potential analytical problems; modifying the immunogenicity of the molecule and leading to potential false negative results. The goal of this article is to provide an overview on the potential technical and analytical challenges in the measurement of cardiac troponins, along with the significance of polymorphisms in the genes encoding for cTnI and cTnT in both health and disease. Clin Chem Lab Med 2009;47:1183-94
Serum bilirubin levels and cardiovascular disease risk - A Janus bifrons? [Review]
No full textThis review examines in vitro and in vivo studies, indicating that bilirubin inhibits lipid oxidation and oxygen radical formation. Experimental and epidemiological evidence is presented that suggests that bilirubin may serve as a physiological antioxidant providing protection against cardiovascular disease. Special attention is focused on large prospective studies that noted a strong, inverse relationship between serum bilirubin concentrations and cardiovascular morbidity and mortality even after adjustment for traditional risk factors. Overall, the evidence from these studies suggests that bilirubin, via its antioxidant potential, has antiatherogenic properties, and that serum bilirubin concentrations in the upper portion of the reference interval for the general population may provide some protection against cardiovascular disease, whereas concentrations in the lower portion of the reference interval indicate increased cardiovascular risk
Association of inflammation with anemia in patients with chronic kidney disease not requiring chronic dialysis.
No full textBackground. Anaemia associated with chronic kidney disease (CKD) has substantial public health importance. However, the association of haemoglobin concentrations with inflammation in the setting of decreased kidney function is not well established. Methods. We analysed cross-sectional data from 7389 outpatient adults, who were referred by general practitioners for routine blood testing between June 2006 and June 2007. Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Multivariable linear regression analysis was used to identify factors independently associated with haemoglobin concentrations across eGFR categories as the main outcome. Results. Of the 7389 participants included in the analytic cohort 2221 (30.1%) participants had eGFR ≥90 mL/min/m2, 4310 (58.3%) 60-89 mL/min/m2 and 858 (11.6%) <60 mL/min/m2. There were significant, graded, increases in high sensitivity C-reactive protein (hs-CRP) and haemoglobin concentrations across eGFR categories independent of age, gender, plasma glucose and lipids (P < 0.0001 for trends). In the multivariable regression analysis, increased hs-CRP concentrations were independently associated with lower haemoglobin concentrations at different stages of eGFR (P < 0.0001 for all). Other independent predictors of lower haemoglobin were older age, female gender and lower eGFR. Conclusions. Our findings suggest that increased plasma hs-CRP concentrations are independently associated with anaemia in the setting of decreased kidney function in a large cohort of unselected adult outpatients. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
Risk of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis: an updated systematic review and meta-analysis of observational studies
No full textPURPOSE: Chronic plaque psoriasis is associated with the presence of non-alcoholic fatty liver disease (NAFLD), but the magnitude of this association remains currently uncertain. We aimed to investigate the magnitude of the association between psoriasis and the risk of prevalent and incident NAFLD, and to assess whether psoriasis severity and/or psoriatic arthritis are associated with a greater risk of NAFLD. METHODS: A systematic review and meta-analysis of observational studies evaluating the association between psoriasis and NAFLD, as diagnosed by imaging or International Classification of Diseases codes was performed. Literature search on PubMed, Scopus and Web of Science on May 3, 2021 was undertaken. Studies using liver biopsy were not available. For the meta-analysis, the random-effects modelling was adopted. RESULTS: We identified 15 observational (case–control and cross-sectional) studies for a total of 249,933 patients with psoriasis (49% with NAFLD) and 1,491,402 controls (36% with NAFLD). Psoriasis was associated with prevalent NAFLD (n = 11 studies; pooled random-effects odds ratio [OR] 1.96, 95% CI 1.70–2.26; I(2) = 97%, p < 0.01). Psoriatic patients with NAFLD had a higher mean psoriasis area and severity index (PASI) than their counterparts without NAFLD (n = 8 studies, pooled weighted mean difference: 3.93, 95% CI 2.01–5.84; I(2) = 88%, p < 0.01). The risk of NAFLD was marginally higher in patients with psoriatic arthritis than in those with psoriasis alone (n = 5 studies, pooled random-effects OR 1.83, 95% CI 0.98–3.43; I(2) = 64%, p = 0.03). Sensitivity analyses did not alter these findings. Funnel plot did not show any significant publication bias. A major limitation of the study was the high degree of heterogeneity across studies. CONCLUSION: Psoriasis is associated with prevalent NAFLD and this risk parallels the severity of psoriasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-022-01755-0
A perspective on metabolic syndrome and nonalcoholic fatty liver disease
No full textNonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed worldwide and is strongly associated with the features of metabolic syndrome. In this brief review, we discuss two key questions relating to NAFLD and metabolic syndrome: (1) Does NAFLD predict the development of type 2 diabetes mellitus and metabolic syndrome, or is it simply an epiphenomenon? (2) Are there differences between metabolic syndrome–associated NAFLD and NAFLD associated with genetic variation in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene? Accumulating evidence indicates that NAFLD is not simply the hepatic manifestation of the metabolic syndrome, but is a pathogenic determinant of the syndrome. Genetic variation within the PNPLA3 gene (e.g., I148M homozygosity) confers a higher risk of developing more severe histological features of NAFLD, but a lower risk of developing metabolic syndrome traits. We suggest that future research is now required to elucidate whether both metabolic syndrome–related NAFLD and PNPLA3-related NAFLD produce the same risk of developing extrahepatic complication
Acquired factor VIII inhibitors in oncohematology: a systematic review.
No full textAcquired hemophilia A is an uncommon but potentially life-threatening hemorrhagic disorder caused by the onset of autoantibodies against coagulation factor VIII. Acquired hemophilia A is most frequently associated with autoimmune diseases, neoplasia, pregnancy and drug reactions but in approximately 50% of the cases no underlying disorder can be identified. A prompt diagnosis of this acquired bleeding disorder is essential for the appropriate management which is aimed to the control of hemorrhage and the suppression of inhibitor. Based on electronic and hand searches of the published literature, this systematic review examines the current knowledge on factor VIII autoantibodies associated with oncohematological disorders. © 2008 Elsevier Ireland Ltd. All rights reserved
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