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Assessment of hepatic fibrosis in MAFLD..a new player in the evaluation of residual cardiovascular risk
No full textAssessment of hepatic fibrosis in MAFLD: a new player in the evaluation of residual cardiovascular risk?
Dear Editor,
We read with great interest the recently published paper by Shonmann Y et al. [1] reporting on an independent positive association between liver fibrosis and ten-year incidence of cardiovascular events (CVEs) in a large sample of community-based general population in Israel. Fibrosis was non-invasively assessed by the FIB-4 score, a simple and well validated score used to rule out (cut-off value ≤1.3) or rule in (cut-off ≥2.67) significant liver fibrosis (F2-F3) [2-3]. These results are of considerable interest since they suggest that hepatic fibrosis could therefore be interpreted as an additional non-lipid marker of residual cardiovascular risk, defined as the risk that remains after the optimal multifactorial treatment of all the coexisting risk factors in the individual.
However, although the Authors emphasize in the Introduction the strong association between non-alcoholic fatty liver disease (NAFLD) and CVEs [4] and the importance to assess cardiovascular risk in this clinical setting, the present study has been performed in the general population, i.e., in a cohort of subjects who did not undergo steatosis assessment, nor evaluation of alcohol intake and of the presence of viral hepatitis B and C.
Prognostic evaluation of fibrosis is of particular importance in patients with NAFLD and even more in those with metabolic associated fatty liver disease (MAFLD) [5], where such an assessment should be mandatory. In fact, it is interesting to note that in Italy, among the NAFLD population, severe hepatic fibrosis (F2-F3) is estimated to involve around 900,000 subjects, mostly asymptomatic, and that this number could reach about one and a half million over the next 10 years [6]. Furthermore, in patients with NAFLD the first cause of death is cardiovascular disease, and the severity of liver fibrosis appears to be the only marker of liver damage capable of predicting the increased cardiovascular risk [4,7].
Our group also found a significant association between non-invasive scores of liver fibrosis - FIB-4 score and NFS (NAFLD fibrosis score) - and CVEs [8], more specifically in patients with NAFLD diagnosis. In fact, we recently published prospectively collected data from 898 patients screened for liver steatosis by ultrasound in the ongoing PLINIO study (Progression of LIver Damage and Cardiometabolic Disorders in Nonalcoholic Fatty Liver dIsease: An Observational Cohort study) in Italy, where the occurrence of cardiovascular events (CVEs) is a secondary pre-specified endpoint [ClinicalTrials.gov no: NCT04036357]. In the study we excluded patients with viral or autoimmune hepatitis and those with history of alcohol abuse and of any other chronic disease. Most patients were overweight and obese, arterial hypertension was present in 58.3%, type 2 diabetes mellitus in 25.7% and metabolic syndrome in 48.6%. Current treatment with statins was present in 38.6%. Almost all patients with NAFLD had diagnostic criteria for MAFLD [5). Incident CVEs included a composite of fatal/nonfatal ischemic stroke and myocardial infarction (MI), cardiac (stent or coronary artery bypass surgery/CABG) or peripheral revascularization (carotid endarterectomy or lower limb percutaneous transluminal angioplasty, PTA), new-onset supraventricular arrhythmias (such as atrial fibrillation) and cardiovascular death. Outcomes were assessed by phone interview every 6 months and by in-person examination every 12 months.
Over a median follow-up time of 41.4 months (3044.4 patient-years), 58 CVEs (1.9%/year) were registered. The rate of CVEs was more than a 2-fold higher in patients with NAFLD (n=643, 2.1%/year) vs those without NAFLD (n=255, 1.0%/year) (P=.066). In multivariable Cox proportional regression analysis, NAFLD increased risk for CVEs (hazard ratio [HR], 2.41; 95% CI, 1.06–5.47; P=.036), after adjustment for metabolic syndrome. The independent predictive value of FIB-4 and NFS for incident CVEs was evaluated in 643 subjects with NAFLD. Among NAFLD patients, FIB-4 >2.67 was independently associated with cardiovascular events (hazard ratio, 4.02; 95% CI, 1.21- 13.38), as was NFS >0.676 (hazard ratio, 2.35; 95% CI, 1.05-5.27). In addition, in our study, metabolic syndrome was also an independent predictor of CVE in NAFLD patients. Of note that an independent association with CVEs was observed also when advanced fibrosis was defined using NFS, a score largely driven by metabolic factors (e.g., diabetes and obesity), which could not be calculated in the study by Shonmann Y et al. [1].
Evidence from the above studies suggests the hypothesis that the development of hepatic fibrosis in patients with MAFLD may be the result of long-term exposure to cardio-metabolic risk factors such as obesity, diabetes, and metabolic syndrome [9]. These conditions can promote insulin resistance, inflammation, lipopolysaccharide translocation and oxidative stress which in turn can induce hepatocellular damage, activation of stellate cells and Kupfer cells with consequent increase in liver fibrogenesis [10] (Fig.1). Hepatic fibrosis could therefore be interpreted as a non-lipid marker of residual cardiovascular risk. Moreover, the great prevalence of MAFLD in the general population and in populations at increased cardio-metabolic risk (diabetes, obesity) strongly suggests monitoring the progression of hepatic fibrosis in a non-invasive way. Finally, the new diagnosis of MAFLD no longer includes the dichotomous condition of NASH or non-NASH [5]. Therefore, in MAFLD patients it is of great importance to assess the severity of fibrosis which represents the most important risk factor both for the progression of liver disease and for the risk of cardio-metabolic complications. The routine use of non-invasive tests will allow the identification of subjects with little or no fibrosis and reasonably exclude the presence of an increased risk for cardiovascular events and serious hepatic complications. On the contrary, the documentation of severe fibrosis may help to identify early subjects at greater risk of liver disease progression and to better define the residual cardiovascular risk
Statins and non-alcoholic fatty liver disease
Full text linkDear Editor,
In April 9 issue, van den Berg et al1 report interesting results on
the indication for lipid‐lowering treatment in a large cohort with
suspected non‐alcoholic fatty liver disease (NAFLD) within the
population‐based Lifelines Cohort Study. Fatty liver index (FLI) ≥60
was used as a proxy of NAFLD and the NAFLD fibrosis score (NFS)
to identify the NAFLD patients with suspected advanced fibrosis.
Cardiovascular disease (CVD) risk was established by the 2016
European society of Cardiology/European Atherosclerosis Society
(ESC/EAS) Guidelines for the Management of Dyslipidemias.2
Subjects with FLI ≥ 60 (suspected NAFLD) had an increased 10‐
year predicted cardiovascular risk compared to those with FLI < 60
with an approximately 2 times higher need for statin therapy based
on CVD risk prediction and their LDL cholesterol level. Subjects with
a FLI ≥ 60 were more likely to be classified with type 2 diabetes,
Metabolic Syndrome (MetS), history of CVD and impaired renal function.
Interestingly, estimated 10‐year very high cardiovascular risk was
approximately 4 times higher in subjects with a NFS > 0.676 compared
to those with the absence of advanced fibrosis. Finally, indication for
statin treatment was positively associated with a FLI ≥ 60 after controlling
for age, sex, current smoking, impaired renal function, and the
presence of MetS and its individual components. The above results
have an even greater relevance if we consider that all the subjects who
were already on statin therapy were subtracted from the analysis.
These findings may have an important clinical relevance and emphasize
the need for effective treatment with statins in patients with
NAFLD. Indeed, accumulating evidence suggests that CVD, rather
than liver disease, dictates the outcomes in NAFLD.3 Besides, in
most subjects NAFLD constitutes the hepatic component of MetS
and numerous patients have atherogenic dyslipidemia.
This study further supports the results of a previous study by our
group where under prescription of statins in patients with NAFLD
was observed.4 In fact, mild liver enzyme elevation remains a concern
and despite its proven efficacy and safety,5 statin administration
is sometimes limited by the worry about related side effects.
Indeed, there is a tendency of general physicians to discourage statin
use in patients with baseline elevation of serum liver enzymes and/
or to discontinue medication when minor alterations were appreciated.
Of note, in our study, statin under‐use was high also in patients
at very high CV risk such as those with a previous CV event.
This study by van den Berg et al further stresses the issue of
under prescription of statins in people with NAFLD and indication
for treatment, based on CV risk class and low‐density lipoprotein
cholesterol target according to ESC/EAS guidelines
Going Beyond Counting First Authors in Author Co-citation Analysis
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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
Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis
Full text linkNon-alcoholic fatty liver disease (NAFLD) is characterised by fatty deposition in the hepatocytes of patients with minimal or no alcohol intake and without ther known cause. NAFLD include a wide spectrum of histologic abnormalities ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), or even cirrhosis. Antioxidant supplements, therefore, could potentially protect cellular structures against oxidative stress and the resulting lipid peroxidation. There is insufficient data to either support or refute the use of antioxidant supplements for patients with NAFLD. It may be advisable to carry out large prospective randomised clinical trials on this topic
Nonalcoholic fatty liver disease and the kidney: a review
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Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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