Non-alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury-related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin-sensitizing agents, anti-oxidants or cytoprotective drugs may be useful, but there is no evidence-based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.

RTP and PEEP can be considered adequate ventilatory settings for morbidly obese patients, without any significant difference with regard to gas exchange improvement. However, the decrease in CO may partially counteract the beneficial effects on oxygenation of these ventilatory settings.

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNα treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNβ and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.Festi D, Sandri L, Mazzella G, Roda E, Sacco T, Staniscia T, Capodicasa S, Vestito A, Colecchia A. Safety of interferon β treatment for chronic HCV hepatitis.

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Background and Aim: Obesity affects cardiovascular risk and also quality of life (QoL). The aim of this study was to test weight loss and impact on QoL after sibutramine treatment in obese subjects. Methods: Double-blind randomized trial on 309 outpatients (51 males, 258 females; age 41.8 ± 10.9 years, BMI 35.0 ± 3.1 kg/m²) randomized to sibutramine (n = 154) or to placebo (n = 155) treatment. A combination of sibutramine 10 mg or matching placebo and a balanced hypocaloric diet was given for 6 months with monthly evaluations. The main outcome measures were weight loss, the impact of weight on QoL, BMI, and waist circumference. Results: The mean weight reduction was 8.2 kg in the sibutramine group and 3.9 in the placebo group at 6 months (p < 0.01). 40% of the sibutramine subjects and 14% of the control subjects lost ≧10% of their body weight (p < 0.01). The improvement in the impact of weight on QoL was statistically significant only in the sibutramine group at 6 months (mean –12.5 vs. –4.5 points; p < 0.01). In the sibutramine group the reduction in BMI (–3.1 vs. –1.4 kg/m²) and waist circumference (7.7 vs. 3.5 cm) was significantly greater (p < 0.001). The incidence of adverse events was low and similar to the placebo. Conclusions: This study confirmed that sibutramine significantly enhances the effect of diet on weight loss, BMI and waist circumference reduction, and showed a significant improvement of QoL.

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