Clinical update on non-alcoholic fatty liver disease and steatohepatitis

clusion of less common causes of fatty liver such as Hepatitis B or C infection, drugs and autoimmune disorders, fatty liver is classified as non-alcoholic (NAFLD) or alcoholic fatty liver disease (AFLD) on the basis of daily ethanol intake. The agreed threshold of ethanol intake used to separate NAFLD from AFLD is 20 g/day, equivalent to 12 drinks per week. 2 The term NAFLD covers a wide spectrum of liver injury, ranging from simple steatosis, i.e. fatty infiltration of hepatocytes > 5%, to non-alcoholic steatohepatitis (NASH). At liver biopsy NASH is characterized by necro-inflammation and/or fibrosis, and is histologically indistinguishable from alcoholic steatohepatitis. The histological classification of NAFLD and NASH is being continuously improved and a refined scoring system has been recently proposed by the National Institutes of Health. 3 NAFLD is presently regarded as the most common liver disease in Western countries and virtually impacts all fields of clinical medicine, being considered a risk factor for advanced liver disease, type 2 diabetes and cardiovascular disease. Although NAFLD had long been recognized as a frequent clinical entity, only recently its importance as a potential cause of progressive and severe liver disease has been fully acknowledged. NAFLD prevalence in the general population ranges from 16 to 25% in adults 4 and from 10 to 19% in children. 5 It increases with age, shows different gender specificity according to geographic areas (generally more prevalent in women in US and viceversa in men in Europe and Japan) and varies with ethnicity, with the highest prevalence among the Hispanic population and the lowest among the AfroAmerican one. 6 Prevalence rates of NAFLD are strikingly increased in certain subpopulations, such as patients with obesity, type 2 diabetes mellitus and dyslipidemia, and the whole spectrum of NAFLD is commonly associated with the metabolic syndrome. The true prevalence of NASH remains largely unknown. According to data derived from autopsy or liver biopsy studies, about 10-15% of NAFLD patients meet the current diagnostic criteria for NASH, pointing to a prevalence of 2-3% in the general population. The incidence and natural course of NAFLD are also difficult to assess because most of the available studies are retrospective and/or performed on clinical series. The few prospective studies are too short to exclude late complications. While simple steatosis has a benign prognosis, NASH may progress to cirrhosis in 30% of cases and is responsible for liver-related death in 3-8%. In clinical series, up to 70% of patients with cryptogenic cirrhosis have clinical features suggestive of NASH. 2