Elevated Serum Alanine Aminotransferase and γ-Glutamyltransferase and Mortality in the United States Population

Background & Aims

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.

Methods

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.

Results

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).

Conclusions

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.

Abbreviations used in this paper: ALT, alanine aminotransferase, BMI, body mass index, CDC, Centers for Disease Control and Prevention, CI, confidence interval, CVD, cardiovascular disease, GGT, γ-glutamyltransferase, HDL, high-density lipoprotein, HR, hazard ratio, ICD, International Classification of Diseases, NCHS, National Center for Health Statistics, NHANES, National Health and Nutrition Examination Survey