Nonalcoholic steatohepatitis (NASH) affects up to 3% of the North American population. It occurs as a manifestation of the insulin-resistant state and oxidative stress is thought to be a key component of its pathophysiology. Exercise and diet, which are the mainstay of therapy, are difficult to achieve and maintain with a disappointing long-term compliance record. There is growing literature on the potential for antioxidant therapy. The recent literature strongly suggests that vitamin E supplementation and other putative free radical scavengers and/or antioxidants are beneficial in improving biochemical and histological parameters in NASH. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) is a clinico-histopathological entity with histological features that resemble alcohol-induced liver injury; but by definition, it occurs in patients with no recent or ongoing significant alcohol consumption (>21 drinks on average per week in men and >14 drinks on average per week in women) [1]. NAFLD is becoming a greater health concern in North America, with increasing rates of obesity and type II diabetes. An insulin-resistant state and the presence of the metabolic syndrome are strongly associated with NAFLD [2, 3]. Up to 30% of the current North American population has NAFLD, with 10% of them having subclinical hepatic inflammation known as nonalcoholic steatohepatitis (NASH) or fibrosis [4]. NAFLD encompasses a spectrum of conditions, starting with isolated hepatic steatosis, progressing to NASH, cirrhosis, and ultimately hepatocellular carcinoma (HCC) [5]. Moreover, there is a growing body of the literature suggests that HCC might occur in the settings of NASH in the absence of cirrhosis [6]. The gold standard of diagnosis is liver biopsy, which has both diagnostic and prognostic value [1]. Macrovesicular steatosis is seen predominantly in zone 3 although it may be panacinar. Hepatocyte ballooning, Mallory bodies, a mixed inflammatory infiltrate, and pericellular fibrosis are additional features typical of NASH [7]. The Brunt classification enables staging of fibrosis in NASH by considering these various histological features [8]. 2. The Role of Oxidative Stress in the Pathogenesis of NASH The pathogenesis of NASH has not been fully elucidated. Currently, the most widely supported theory in the pathogenesis of NASH is a “two-hit” theory. According to this theory, the “first hit” involves fat accumulation in the hepatocytes, where insulin resistance is suggested to be the key pathogenic factor [9, 10]. Insulin resistance, found in obesity and type 2
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