1,721,547 research outputs found
Of liver, whisky and plants: A requiem for colchicine in alcoholic cirrhosis?
No full textColchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications
Is insulin resistance a pathogenetic co-factor in HCV-related disease and hepatocellular carcinoma?
No full text(Letter
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
The potential for statins in the chemoprevention andmanagement of hepatocellular carcinoma.
No full textHepatocellular carcinoma (HCC) is a common, treatment-resistant malignancy with a complex molecular pathogenesis. Statins are a widely used class of cholesterol-lowering drugs with potentially anticancer activity. We reviewed the evidence for a role of statins in primary and secondary chemoprevention of HCC and slowing the course of otherwise incurable primary or recurrent disease. A literature search (Key-words Statins; hepatocellular carcinoma) conducted to this end, retrieved 119 references. Here we summarize history, mechanism of action and cardiovascular use of statins and highlighted that statins can affect several pathways implicated in the development of HCC. In vitro and animal studies provide strong evidence for a favourable effect of statins on HCC. However evidence in humans is conflicting. We discuss in full detail the methodological strengths and pitfalls of 3 cohort studies suggesting that use of statins may protect from the development of HCC and of a single trial reporting increased survival in those with advanced HCC randomized to. Statins, a remarkably hepato-safe class of drugs acting on both hepatocyte and endothelial cells, also have potentially beneficial effects in lowering portal hypertension. In conclusion, there is strong experimental evidence that statins are beneficial in chemopreventing and slowing the growth of HCC. However, randomized controlled trials are necessary in order to investigate the role of statins in the chemoprevention of HCC and in slowing the course of otherwise incurable disease in humans
If steatosis is the atherosclerosis of the liver, are statins the "aspirin" for steatosis?
No full textNot availabl
An approximate mean value analysis approach for system management and overload control
No full textBlocking is the phenomenon where a service request is momentarily stopped, but not lost, until the service becomes available again. Despite its importance,
blocking is a difficult phenomenon to model analytically, because it creates strong inter-dependencies in the systems components. Mean Value Analysis (MVA) is one of the most appealing evaluation methodology since its low computational cost and easy of use. In this paper, an approximate MVA for Bloking
After Service is presented that greatly outperforms previous results. The new algorithm is obtained by analyzing the inter-dependencies due to the blocking
mechanism and by consequently modifying the MVA equations. The proposed algorithm is tested and then applied to a capacity planning and admission control
study of a web server system
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