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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is increasing in frequency the USA. Age-adjusted incidence, hospitalization, and mortality rates have doubled over the past two decades. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age 65), there has been a considerable shift toward younger cases. There is a birth cohort effect with those born after 1945. Men are affected three times more frequently than women, Asians two times more than African American and Hispanic people, who are affected two times more often than Caucasians. However, the recent increase has disproportionately affected Caucasian (and Hispanic) men between ages 45 and 65. Hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely tocontinue to increase for the next decade. A variable but significant proportion of cases (15-50%) do not have evidence for the risk factors of either viral hepatitis or heavy alcohol consumption. Insulin resistance syndrome manifesting as obesity and diabetes is emerging as a risk factor for HCC in the USA and may operate through the formation of non-alcoholic fatty liver disease (NAFLD); however, its effect on the current trend in HCC remains unclear. While there has been a small recent improvement in survival, it remains generally dismal (median 8 months). Population-based data in the USA indicate low application rate of HCC potentially curative therapy and marked regional differences.
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PMID:Epidemiology of hepatocellular carcinoma in USA. 1787 2

Clinical guidelines highlight the importance of dyslipidaemia management for reducing the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome. While statins represent the main focus of therapy, there is increasing evidence that the addition of a fibrate such as fenofibrate provides further reduction in risk. Fenofibrate also offers a number of benefits beyond lipid modification; these are mediated by peroxisome proliferator-activated receptor-alpha (PPARalpha) activation and appear to be independent of effects of glucose and lipid metabolism. Furthermore, as shown by the Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study, fenofibrate treatment has promising effects in preventing progression of diabetes-related microvascular complications. PPARalpha is critical to lipid metabolism in the liver. Recent findings which showed that pioglitazone, a PPARgamma agonist with weak PPARalpha activity, improved fatty liver disease in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome or type 2 diabetes have prompted interest in whether more potent PPARalpha agonists, such as fenofibrate, may have a role in the management of non-alcoholic fatty liver disease (NAFLD). The combination of fenofibrate and a statin is well tolerated, with no apparent increase in the risk of myopathy, unlike gemfibrozil-statin combination therapy. In overview, the available evidence indicates that the combination of fenofibrate with a statin is a useful approach for optimising reduction in the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome, as well as delaying the progression of diabetes-related microvascular complications. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of this approach.
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PMID:The role of fenofibrate in clinical practice. 1793 56

The correlation between biochemistry, imaging-studies and histology is a matter of controversy in non-alcoholic fatty liver disease (NAFLD) and the major pathophysiology of non-alcoholic steatohepatitis (NASH) is still unknown. We aimed to perform a comparative analysis between clinical, biochemical and histological variables of NAFLD. One-hundred and five NAFLD patients (F/M: 51/54), were studied, all with no-alcohol intake. The groups were followed-up for six months. Necroinflammation and fibrosis were more severe in patients with diabetes (p = 0.002, and p = 0.0001, respectively). In comparing NAFL to NASH, plasma nitric-oxide and malondialdehyde levels were significantly higher (p = 0.05, for-both), and vitamin-E and-C levels were significantly lower in NASH (p = 0.002, and 0.001, respectively). The serum ferritin levels were higher in NASH patients (p = 0.016). While the ultrasonographic grade was significantly higher, the liver-spleen density gradient was significantly lower in NASH group (p = 0.017, and 0.005, respectively). Within a six month period, serum ALT levels dropped into the normal range in 23/76 (30.3%) patients and serum ALT in the 6th month correlated significantly with the severity of steatosis, inflammation and fibrosis in initial biopsy (p = 0.023, 0.035, 0.011, respectively). In conclusion, the probability of severe liver disease is higher in patients with elevated-ALT in NAFLD. Serum ferritin levels have some prognostic significance in liver damage and fibrosis. Overt diabetes is predictive of advanced fibrosis and inflammation. However impaired glucose-tolerance is not. The advice on diet and exercise for six months after diagnosis may be a good strategy in NAFLD. The patients with normal-ALT without hepatomegaly, morbid-obesity and diabetes seem to have a good prognosis, however some of these patients may still require liver biopsy.
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PMID:Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease. 1807 37

Phenolic compounds are widely present in the plant kingdom. Many epidemiological studies have indicated that consumption of some plant-derived foodstuffs with high phenolic content is associated with the prevention of some diseases and that these compounds may have similar properties to antioxidants, antimutagenic agents, antithrombotic agents, anti-inflammatory agents, anti-HIV-1, and anticancer agents. However, obesity is an important topic in the world of public health and preventive medicine. Relationships between body mass index, waist circumference, or waist-to-hip ratio and the risk of development of some diseases (such as heart disease, dyslipidemia, hypertension, non-alcoholic fatty liver disease, diabetes, kidney failure, cancer, stroke, osteoarthritis, and sleep apnea) have been observed. Evidence that phenolic compounds have beneficial effects in fighting obesity is increasingly being reported in the scientific literature. These in vitro and in vivo effects of phenolic compounds on the induction of pre-adipocytic and adipocytic apoptosis and inhibition of adipocytic lipid accumulation are considered in detail here. This review presents evidence of their inhibitory effects on obesity and their underlying molecular signaling mechanisms.
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PMID:Phenolic compounds: evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. 1808 Dec 7

This review considers the value of monitoring inflammatory markers as a guide to selecting appropriate drugs in patients at high risk of cardiovascular disease (CVD). Clinical and experimental studies investigated inflammation in patients with acute coronary syndromes (ACS), stable coronary artery disease (CAD) and diabetes mellitus (DM) or metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) or systemic autoimmune diseases (SAD). Evidence suggests that in these high risk groups inflammation plays a role in the extent and severity of atherosclerosis. Simple inflammatory markers (e.g. C-reactive protein and fibrinogen) can be monitored cost effectively and may influence the selection of drugs that can normalize both traditional CVD risk factors and inflammation. However, this concept requires proof in appropriately designed trials that include clinically relevant end points.
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PMID:Do we need to consider inflammatory markers when we treat atherosclerotic disease? 1842 Feb 11

GH therapy was approved in 2006 for treatment of adult growth hormone deficiency (GHD) in Japan. Until then, GH was used only to treat short stature in children with GHD and the treatment was stopped when the final height was reached. In the present study, we investigated metabolic co-morbidities experienced by adults with childhood-onset (CO) GHD after the cessation of GH. Forty-two patients with COGHD (M/F 22/20, age at follow up when the retrospective analysis was carried out: 18-52 yr) treated with GH in childhood were studied. We reviewed the medical records of these patients to determine the metabolic co-morbidities that developed after cessation of GH. The median age was 19 yrs (range: 14-38) at cessation of GH, and the following co-morbidities were observed: hypertriglyceridemia in 15 (41%) patients, non-alcoholic fatty liver disease (NAFLD) in 11 (29%) patients, hypercholesterolemia in 10 (26%) patients, diabetes mellitus (DM) in 4 (10%) patients, and hypertension in 1 (2.4%) patient. The median BMI when these complications became overt was 23.5 kg/m(2) for those with hypertriglyceridemia, 26.0 kg/m(2) for those with NAFLD, 20.9 kg/m(2) for those with hypercholesterolemia, and 27.2 kg/m(2 ) for those with DM. More than two co-morbidities were experienced by 32% of men and 30% of women. In conclusion, adults with COGHD after the cessation of GH have multiple metabolic co-morbidities. Lifelong GH replacement might be important for improving the overall metabolic profiles in these patients.
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PMID:Metabolic co-morbidities revealed in patients with childhood-onset adult GH deficiency after cessation of GH replacement therapy for short stature. 1861 81

The global increase in the prevalence of obesity has heralded a rise in associated liver injury namely NAFLD (non-alcoholic fatty liver disease). It is estimated that 20-30% of adult populations in developed countries have NAFLD and, although high quality data is currently lacking, the condition is clearly increasing in children also. NAFLD should be suspected in those with commonly available simple clinical signs and biochemistry consistent with insulin resistance. A small number of individuals with NAFLD, often considered a relatively benign condition, will progress to more severe stages of liver disease including NASH (non-alcoholic steatohepatitis) with or without fibrosis, cirrhosis and occasionally hepatocellular carcinoma. NAFLD is also commonly associated with an increased risk of developing Type 2 diabetes and treatable features of insulin resistance such as dyslipidaemia and dysglycaemia. Histological examination of liver tissue remains the only proven method to distinguish between simple steatosis and NASH, a condition far more likely to progress to cirrhosis. Identification of an imaging technique or non-invasive marker to achieve this distinction is therefore much sought after and would allow larger clinical trials and better clinical assessment. Case series and pilot studies of lifestyle advice, insulin sensitizers and other medications have shown improvements in liver histology and serum liver enzymes but robust randomized controlled studies are needed. Furthermore, the cost/benefit ratio of any new therapies, and any potential harms, must be evaluated carefully before being clinically advocated.
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PMID:Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. 1866 68

Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, atherosclerosis, and non-alcoholic fatty liver disease. The evidence that obesity can be regarded as an inflammatory disease comes from numerous studies showing a moderate increase of circulating inflammatory factors in obese patients and the identification of different types of immune cells infiltrating the human adipose tissue. Obesity may induce a pro-inflammatory state, which can cause or worsen insulin resistance in adipose tissue, skeletal muscle, and liver. The causative factors of this inflammation process in obesity are not entirely understood, but adipose tissue seems to play an important role in the relationship between obesity and chronic inflammation. Increased infiltration of adipose tissue with immune cells could cause adipose tissue insulin resistance via autocrine and paracrine cytokine/adipokine signalling, which contributes to systemically decreased insulin sensitivity via endocrine signalling. On the other hand, obesity-induced inflammation could represent a compensatory mechanism for increased adipose tissue turnover in obese states, which might protect obese individuals against deleterious effects of fat accumulation. A better understanding of the mechanisms and molecular components of obesity induced inflammatory response might lead to identifying novel therapeutic targets to prevent obesity-related complications.
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PMID:The inflammatory process of adipose tissue. 1880 22

An association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has been recently suggested. Indeed, different studies have demonstrated that NAFLD patients present increased subclinical atherosclerosis compared to non-steatosic individuals, and are supported by the few follow-up studies revealing that CVD is the second most common cause of death in NAFLD patients. However, the nature of the relationship NAFLD/CVD is still under debate: is NAFLD a consequence of, or a contributor to, the dysmetabolic cascade leading to atherosclerosis? In this issue of the journal, McKimmie and coauthors analyzed a subset of 623 participants from the Diabetes Heart Study for hepatic steatosis, classic CVD risk factors, subcutaneous and visceral fat, coronary, aortic and carotid artery calcium, and carotid intima-media thickness. After adjusting for all the CVD risk factors plus visceral fat, they did not find independent associations between steatosis and the cardiovascular markers of interest, and conclude that NAFLD may be best described as an epiphenomenon in this context. The strength of this study resides in the numerosity of the sample, the broad cardiovascular examination, and the direct assessment by computed tomography of visceral fat, an undisputed major contributor to NAFLD, the metabolic syndrome and atherosclerosis. However, waiting for prospective and interventional studies in order to definitely determine the nature of the relationship NAFLD/CVD, sufficient evidence exists to derive a first message and transfer it into the clinical practice: an overall assessment of the CVD risk, and the aggressive management of the atherosclerotic risk factors, seem mandatory in all NAFLD patients.
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PMID:Association between non-alcoholic fatty liver disease and cardiovascular disease: a first message should pass. 1885 70

As little as 10 years ago, there was scepticism as to weather non-alcoholic fatty liver disease is a clinical condition. With the increasing prevalence of obesity, diabetes mellitus and the metabolic syndrome in the general population, non-alcoholic fatty liver disease has become a household diagnosis in clinical practice of several medical specialities. Meanwhile, it is the primary cause for elevated liver enzymes of unknown cause in clinical practice. Treatment is focused on the improvement of insulin resistance and of antioxidative mechanisms, mainly by life-style modifications including weight loss and exercise. Drug therapy cannot be recommended at this time, because studies showing positive effects on morbidity and mortality are still lacking. In addition, issues concerning long term safety and side effects of drugs still have to be resolved.
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PMID:[Are there therapeutic approaches of non-alcoholic fatty liver disease and its complications?]. 1900 23


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