Elevated serum alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) activities are markers of liver injury, but may also be associated with other diseases and death. In a prospective, national, population-based sample, we examined whether elevated ALT and GGT were associated with increased risk of all-cause and disease-specific mortality.

Death certificate–based 12-year mortality was analyzed among 14,950 adult participants in the third US National Health and Nutrition Examination Survey, 1988–1994, who were negative for markers of viral hepatitis B and C. Abnormal ALT was defined as >30 U/L in men or >19 U/L in women, and abnormal GGT as >51 U/L in men or >33 U/L in women.

Cumulative mortality was 13.9% from all causes, including 4.2% from cardiovascular disease, 4.2% from neoplasms, 0.44% from diabetes, and 0.13% from liver disease. In multivariate-adjusted analyses, elevated ALT was not associated with all-cause mortality (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.88–1.6). ALT elevation was associated with deaths from liver disease (HR, 8.2; 95% CI, 2.1–31.9), but not from cardiovascular disease (HR, 0.90; 95% CI, 0.56–1.4), neoplasms (HR, 1.0; 95% CI, 0.65–1.5), or diabetes (HR, 2.4; 95% CI, 0.65–9.1). All-cause mortality increased with elevated GGT (HR, 1.5; 95% CI, 1.2–1.8), as did mortality from liver disease (HR, 13.0; 95% CI, 2.4–71.5), neoplasms (HR, 1.5; 95% CI, 1.01–2.2), and diabetes (HR, 3.3; 95% CI, 1.4–7.6), but not from cardiovascular disease (HR, 1.3; 95% CI, 0.80–2.0).

In the US population, elevated GGT was associated with mortality from all causes, liver disease, cancer, and diabetes, while ALT was associated only with liver disease mortality.