P Hůlek1, I Dresslerová. 1. II. Interní klinika Lékarské fakulty UK a FN Hradec Králové. hulek@fnhk.cz
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition of excess fat deposition within the liver. NAFLD includes a spectrum of liver pathology ranging from bland hepatic steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrosing condition of the liver thought to be an intermediate stage of NAFLD that may progress to endstage liver disease, liver-related death and hepatocellular carcinoma. Nonalcoholic steatohepatitis (NASH) is a common liver disease that is characterized histologically by hepatic steatosis, lobular inflammation, and hepatocellular ballooning, it can progress to cirrhosis in up to 15% of patients. There is currently no therapy that is of proven benefit for nonalcoholic steatohepatitis. The disease is closely associated with insulin resistance and features of the metabolic syndrome such as obesity (increased waist circumference), hypertriglyceridemia, and type 2 diabetes. The pathologic criteria are now well established and the diagnosis can only be made once the absence or limited use of alcohol is confirmed. In addition to insulin resistance, oxidative stress has been implicated as a key factor contributing to hepatic injury in patients with nonalcoholic steatohepatitis. Thus, both insulin resistance and oxidative stress are attractive targets for therapy in patients with this disease. Several pilot studies have provided evidence that insulin sensitizers such as thiazolidinediones and antioxidants such as vitamin E improve clinical and histologic features of nonalcoholic steatohepatitis. The medical evidence of a benefit, however, is limited, because these studies had small samples and were performed at single centers. Moreover, a recent multicenter trial showed a reduction in hepatic steatosis but no improvement in markers of cell injury after a year of rosiglitazone therapy. The value of these remains uncertain. Until now the best trial was done by Sanyal, who studied 240 patients divided into 3 groups (pioglitazone versus vitamin E versus placebo)--multicenter, randomized, double-blind clinical trial in non-diabetics.
RCT Entities:
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition of excess fat deposition within the liver. NAFLD includes a spectrum of liver pathology ranging from bland hepatic steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrosing condition of the liver thought to be an intermediate stage of NAFLD that may progress to endstage liver disease, liver-related death and hepatocellular carcinoma. Nonalcoholic steatohepatitis (NASH) is a common liver disease that is characterized histologically by hepatic steatosis, lobular inflammation, and hepatocellular ballooning, it can progress to cirrhosis in up to 15% of patients. There is currently no therapy that is of proven benefit for nonalcoholic steatohepatitis. The disease is closely associated with insulin resistance and features of the metabolic syndrome such as obesity (increased waist circumference), hypertriglyceridemia, and type 2 diabetes. The pathologic criteria are now well established and the diagnosis can only be made once the absence or limited use of alcohol is confirmed. In addition to insulin resistance, oxidative stress has been implicated as a key factor contributing to hepatic injury in patients with nonalcoholic steatohepatitis. Thus, both insulin resistance and oxidative stress are attractive targets for therapy in patients with this disease. Several pilot studies have provided evidence that insulin sensitizers such as thiazolidinediones and antioxidants such as vitamin E improve clinical and histologic features of nonalcoholic steatohepatitis. The medical evidence of a benefit, however, is limited, because these studies had small samples and were performed at single centers. Moreover, a recent multicenter trial showed a reduction in hepatic steatosis but no improvement in markers of cell injury after a year of rosiglitazone therapy. The value of these remains uncertain. Until now the best trial was done by Sanyal, who studied 240 patients divided into 3 groups (pioglitazone versus vitamin E versus placebo)--multicenter, randomized, double-blind clinical trial in non-diabetics.