Evaluation and management of non-alcoholic steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases characterized mainly by macrovesicular steatosis (Fig. 1) that occurs in the absence of alcohol consumption in amounts considered injurious to the liver. The hepatic histology can vary from isolated hepatic steatosis alone to steatohepatitis and are referred to as nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) respectively. In addition to predominantly macrovesicular steatosis, the diagnosis of steatohepatitis also requires the additional presence of varying combinations of findings including cytologic ballooning, Mallory’s hyaline, scattered inflammation and pericellular fibrosis (Fig. 1) [1]. These findings are indistinguishable from alcoholic liver disease and the distinction must be made clinically. A large body of literature clearly indicates that NAFLD is strongly associated with the metabolic syndrome. Early studies identified obesity and diabetes as the two major risk factors for the development of NAFLD [2]. It is now known that hypertriglyceridemia and hypertension are also frequently present in subjects with NAFLD. The metabolic syndrome is characterized by a constellation of findings including obesity, diabetes, hypertension and hypertriglyceridemia, the principal risk factors for NAFLD (Table 1) [3]. The fundamental pathophysiologic process that connects these diverse conditions is insulin resistance [4]. Insulin resistance is present in approximately 98% of individuals with NAFLD and over 80% of subjects with NAFLD meet minimal criteria for the metabolic syndrome [5]. Approximately 47 million individuals are estimated to have the metabolic syndrome in the US [6]. Also, over 50% of the US population is overweight (body mass index (BMI) O25!29) or obese (BMI O29) [7]. There are thus millions