Dangerous Liaisons: The Metabolic Syndrome and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is an underrecognized manifestation of the metabolic syndrome. The term refers to a spectrum of fatty liver disease that occurs in the absence of significant alcohol consumption. At the “benign” end of the spectrum, most patients with NAFLD have fatty liver alone (simple steatosis). Only a small proportion (approximately 10%) also have features of liver cell injury or fibrosis, referred to as nonalcoholic steatohepatitis (NASH). This distinction between simple steatosis and NASH is important because the natural history of these categories differs substantially. Patients with simple steatosis usually have a benign prognosis from the point of view of liver disease (1-4). In contrast, up to 20% of patients with NASH may ultimately develop advanced liver disease (1, 3-5). The prognosis of NASH-related cirrhosis is poor: It results in liver failure or liver-related death in approximately one third of cases (6, 7). Hepatocellular cancer is also a recently recognized complication of NASH-related cirrhosis (6, 8).

Although only a minority of patients with NAFLD develop advanced liver disease, this condition is causing increasing alarm because of its marked prevalence. A recent large population-based study from the United States found a prevalence of hepatic steatosis of 34% (9). However, NAFLD is not just a “western” disease. Increasing rates of NAFLD are being reported in the Asia-Pacific area and have been attributed to the epidemic of obesity and type 2 diabetes spreading throughout this region (10). Data from cross-sectional studies have shown that NAFLD is associated with insulin resistance, which is a key factor driving the development of steatosis (11). The pathogenesis of steatohepatitis and …