Noninvasive Fatty Liver Markers Predict Liver Disease Mortality in the US Population

Nonalcoholic fatty liver disease (NAFLD) contributes to premature death along with obesity, diabetes, and cardiovascular disease (CVD). We examined whether hepatic steatosis (HS) on ultrasound and liver enzyme activities were associated with increased liver disease mortality in the U.S. National Health and Nutrition Examination Survey (NHANES), 1988-1994, with up to 23 years of linked-mortality data. Survey-linked National Death Index records were analyzed among 14,527 adult participants who were negative for viral hepatitis B and C and iron overload. HS on ultrasound was categorized as normal, mild, moderate, or severe. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) elevation was defined as the highest sex-specific decile. Cumulative mortality was 36.2% from all causes, including 16.3% from CVD, 10.8% from cancer, 5.4% from diabetes, and 1.1% from liver disease. Severe HS was associated with increased liver disease mortality in both age-adjusted (hazard ratio [HR]: 3.92; 95% confidence interval [CI]: 1.49-10.27; P for trend: 0.011) and multivariate-adjusted analyses (HR, 2.68; 95% CI: 1.02-7.03; P for trend: 0.072). HS was not independently associated with mortality from all causes, CVD, cancer, or diabetes. Higher liver disease mortality was found with elevated ALT (HR, 4.08; 95% CI: 1.99-8.33), AST (HR, 4.33; 95% CI: 2.18-8.59), and GGT (HR, 7.91; 95% CI: 3.06-20.46). GGT elevation was associated with increased overall mortality (HR, 1.45; 95% CI: 1.21-1.74). Liver enzymes were otherwise unrelated to overall or cause-specific mortality. Conclusions: In the U. S. population, severe hepatic steatosis on ultrasound and liver enzyme elevation were associated with increased liver disease mortality, but were not independently associated with mortality from all causes (except for GGT), CVD, cancer, or diabetes.