The Spectrum of Nonalcoholic Fatty Liver Disease

Nonalcoholic steatohepatitis (NASH) is a condition histologically similar to alcoholic steatohepatitis, yet while the latter has long been recognized as a cause of end-stage liver disease, the former was, until recently, discounted as having a benign course [1–3]. Indeed, it was felt that undisclosed alcohol use must account for those individuals with advanced fibrosis and steatohepatitis [4]. The first histologic account of a condition similar to alcoholic liver injury was made by Ludwig et al in 1980, at which time the term NASH was coined [5]. The condition is often first encountered as asymptomatic liver enzyme elevations or incidentally discovered fatty infiltration on ultrasound [6]. Liver enzymes do not necessarily correlate with the degree of underlying fibrosis [3]. There is a spectrum of disease ranging from asymptomatic steatosis to NASH to advanced liver disease [6,7]. The term nonalcoholic fatty liver disease (NAFLD) has been suggested to encompass both asymptomatic steatosis and steatohepatitis [6,8]. NAFLD is currently the most common clinical problem encountered by hepatologists and, with obesity reaching epidemic proportions, can be expected to increase further in significance [6]. The current estimated prevalence of NAFLD is about 20% [9–14], and the prevalence of NASH is about 5% [14]. Cirrhosis may be found in up to 1 out of 4 individuals with NASH [3]. Recent evidence suggests that NASH may account for a majority of individuals previously diagnosed with cryptogenic cirrhosis [15–17], and this diagnosis accounts for 7% to 14% of liver transplants performed [18,19]. There is currently no effective proven medical therapy for NASH [20,21]. Current treatment strategies focus on lifestyle modification, treatment of underlying risk factors, and avoidance of potential hepatotoxins [21]. A “metabolic syndrome” consisting of obesity, diabetes, hypertension, and hyperlipidemia has been associated with NASH and represents the potentially correctable risk factors for progression [3,22–24].