Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population.
OBJECTIVE
Elevated serum alanine aminotransferase (ALT) and gamma-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.
Ruhl
Constance E
CE
Social & Scientific Systems, Inc, Silver Spring, Maryland 20910, USA. cruhl@s-3.com
Everhart
James E
JE
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D003920:Diabetes Mellitus / Q000097:blood / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000097:blood / Q000401:mortality*; D009749:Nutrition Surveys; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D005723:gamma-Glutamyltransferase / Q000097:blood*
D015415:Biomarkers; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase