Correcting for challenging confounding factors

U ni ve rs ity o f C al ifo rn ia , S an D ie go , C A . Hepatic steatosis, the intracellular accumulation of triglycerides (triglyceride fat) in hepatocytes, is a common and often asymptomatic condition. An estimated 20 to 80 million Americans have nonalcoholic fatty liver disease (NAFld), which is the most common chronic liver disease in the united States.1 Steatosis is now recognized to play a causative role in important hepatic and systemic metabolic disorders. For example, recent data have shown that 5% to 15% of patients with NAFld present with established cirrhosis on liver biopsy and that 4% to 5% of individuals with isolated steatosis eventually develop cirrhosis. the risk of developing cirrhosis is significantly higher in nonalcoholic steatohepatitis (NASH), the aggressive subset of NAFld characterized by the presence of inflammation and fibrosis, in addition to steatosis.2 in other studies, 20% to 50% of individuals with steatosis subsequently became diabetic,3,4 suggesting a causative role of steatosis in the development of type ii diabetes. Recent studies also demonstrate that NAFld is an independent risk factor for cardiovascular mortality beginning at age 45.5 Finally, there is emerging evidence of a relationship between hepatic steatosis and an increased risk of malignancy— 7% of patients with NAFld-related cirrhosis developed hepatocellular carcinoma (HCC) over a 10-year timeframe.6 Because of the high prevalence of NAFld in the general population, it is estimated that more than 50,000 Americans might eventually develop NAFld-related HCC.7