The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy-proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy;
(2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x-ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3-[ 3 H] glucose); ( 5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3-[ 3 H] glucose infusion 3 FPI) and adipose tissue (fasting FFA 3 FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 6 2% vs. 24 6 2%, p 5 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis. Conclusion: When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long-term studies are needed to define their risk of disease progression. (HEPATOLOGY 2011;54:837-845) N onalcoholic fatty liver disease (NAFLD) represents a broad spectrum of clinical and histopathological manifestations, ranging from mild hepatic steatosis through nonalcoholic steatohepatitis (NASH), to fibrosis and ultimately cirrhosis and hepatocellular carcinoma. 1 NAFLD is frequently associated with obesity, insulin resistance, dyslipidemia, and type 2 diabetes mellitus (T2DM), all of which are components of the metabolic syndrome (MetS). 2 However, not all individuals with MetS develop hepatic steatosis, nor do all individuals with hepatic steatosis develop NASH or cirrhosis. 3 Thus, the factors leading to steatosis and steatohepatitis in humans remain poorly understood.