No abstract

No abstract

No abstract

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with Free

No abstract

Although evidence suggests the link between chronic inflammation and oxidative stress as the main mechanism responsible for endothelial dysfunction and cardiovascular complications in patients with metabolic syndrome, little is known about the determining role of each metabolic syndrome component in such alterations. This study investigated the relation between systemic oxidative alterations and metabolic syndrome features in 41 patients. Compared with control subjects, serum vitamin C and alpha-tocopherol concentrations were lower and those of lipid peroxides [thiobarbituric acid reactive substances (TBARs)] were higher in metabolic syndrome patients (P < 0.001). A linear relation was observed between visceral fat thickness and serum TBARs:cholesterol ratio (r = 0.541, P < 0.001), whereas negative correlations were found between alpha-tocopherol and BMI (r = -0.212, P < 0.05) and the grade of liver steatosis (r = -0.263, P < 0.02). Patients with metabolic syndrome and liver steatosis had higher serum hyaluronate (HA) concentrations (P < 0.001). Serum HA was positively correlated with serum alanine amino transferase (r = 0.715, P < 0.001) and the homeostasis monitoring assessment index (r = 0.248, P < 0.03). The presence of metabolic syndrome was predicted from a linear combination of visceral fat and all oxidative variables. In metabolic syndrome patients, serum nitrosothiols and vitamin C concentrations, which were lower (P < 0.001) than in control subjects, were inversely related to the grade of hypertension (r = -0.645, P < 0.001 and r = -0.415, P < 0.007, respectively). In conclusion, metabolic syndrome patients exhibited decreased antioxidant protection and increased lipid peroxidation. Our results indicate a strong association between increased abdominal fat storage, liver steatosis, and systemic oxidative alterations in metabolic syndrome patients and diminished nitrosothiols and vitamin C concentrations as important factors associated with hypertension in these patients.

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.

Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation. 47:2112-2126 G allstones are one the most common gastrointestinal diseases that require hospitalization in the western world, 1 and this is a true health burden 2-4 with enormous costs estimated at 6.5 billion dollars each year in United States. 4,5 Because life expectancy and the incidence rate of obesity are both rising worldwide, 6 the incidence rate of gallstones may increase, often in the context of the "metabolic syndrome". 7 The estimated prevalence of gallstones is 10%-15% in the general population of developed countries. In the United States, approximately 20 million to 25 million adults have gallstones. The burden of the disease is highest (60%-70%) in American Indians followed by Hispanics of mixed Indian origin. In contrast, the rate is lowest (less than 5%) in Asian and African populations. 5 The prevalence is intermediate (10%-15%) in Caucasians in developed countries. In Europe, the Multicenter Italian Study on Cholelithiasis (MICOL) ultrasonographic survey, which was performed across Italy including 29,000 subjects aged 30-69 years, reported an overall prevalence rate of 18.8% and 9.5% in women and men, respectively. 8 Major risk factors for the development of gallstones have been better identified over the past years and include age, female sex, some genetic polymorphisms within a background of a complex genetic disorder, pregnancy, obesity and rapid weight loss on low caloric diets or fol-