Gastroenterology

Gastroenterology

Volume 136, Issue 2, February 2009, Pages 477-485.e11
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Elevated Serum Alanine Aminotransferase and γ-Glutamyltransferase and Mortality in the United States Population

https://doi.org/10.1053/j.gastro.2008.10.052Get rights and content

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.

Section snippets

Methods

NHANES III was conducted in the United States from 1988 through 1994 by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC).21 It consisted of interview, examination, and laboratory data collected from a complex multistage, stratified, clustered probability sample of the civilian, noninstitutionalized population aged 2 months and older, with oversampling of the elderly, non-Hispanic blacks, and Mexican Americans. The study was approved by the

ALT

The prevalence (±SE) of elevated ALT was 13.5% (±0.77%). Compared with participants with normal ALT, those with ALT elevation were younger and more likely to be Mexican American, obese, diabetic, lighter smokers, and less physically active, and to have a central fat distribution; higher total cholesterol, diastolic blood pressure, serum transferrin saturation, and prevalence of elevated C-reactive protein; and a lower HDL cholesterol and caffeine intake, but did not differ significantly with

Discussion

For ALT, the key finding of this study was the lack of an association with overall or CVD mortality in a large, national, population-based, prospective study. This was a consistent finding in both age-adjusted and multivariate-adjusted analyses. Few studies have performed similar analyses, and their results have been inconsistent and not comparable to those of the current study. A large Korean study found a strong association of all-cause mortality with ALT in men, but not women. It did not

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    Supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G).

    The authors disclose no conflicts.

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