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Elevated Liver Enzymes and Mortality in Older Individuals: A Prospective Cohort Study

Mahady, Suzanne E. MBBS, MMed, BMedSci; Wong, Germaine PhD; Turner, Robin M. PhD; Mitchell, Paul PhD; Macaskill, Petra PhD; Craig, Jonathan C. PhD; George, Jacob PhD

Journal of Clinical Gastroenterology: May/June 2017 - Volume 51 - Issue 5 - p 439–445
doi: 10.1097/MCG.0000000000000622

Aim of the study: The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)].

Methods: We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up.

Results: Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30).

Conclusions: In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age.

*School of Public Health

Storr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney

Centre for Kidney Research, Kids Research Institute, Children’s Hospital at Westmead, Sydney

§School of Public Health and Community Medicine, University of New South Wales, Kensington

Centre for Vision Research, Westmead Millennium Institute and University of Sydney, Sydney, NSW, Australia

S.E.M. is supported by a National Health and Medical Research Council of Australia (NHMRC) Postgraduate Research Scholarship. J.G. is supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney, and grants from the NHMRC (1053206, 632630, and 1049857).

The authors declare that they have nothing to disclose.

Address correspondence to: Suzanne E. Mahady, MBBS, MMed, BMedSci, Sydney School of Public Health, Edward Ford Building, A26, Room 332, University of Sydney, Camperdown, Sydney, NSW 2006, Australia (e-mail:

Received February 10, 2016

Accepted June 25, 2016

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