Elevated Liver Enzymes in Routine Care Hint at Impending Early Mortality


By Judith Groch
ROCHESTER, Minn., March 5 -- High serum aminotransferase levels discovered during routine medical care were associated with an increased risk of death in the next decade, a population-based study found.
Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) predicted progressive decreases in survival, with an increase in mortality from 21% to 78%, W. Ray Kim, M.D., of the Mayo Clinic here, and colleagues reported in the March issue of Hepatology.
Studies in other countries have shown that elevated liver enzymes are associated with early mortality, but the connection has never been examined in a U.S. population, Dr. Kim and colleagues said.
The findings came from a study of all adult residents (mainly white) in Olmsted County, Minn., in 1995. Most of these patients received medical care at Mayo Clinic facilities. Their AST or ALT results, when available from routine visits, were extracted from a laboratory database.
To determine survival, the patients were followed from January 1995 to April 2006. To eliminate patients with abnormal results because of a terminal illness, deaths within the first two years were excluded. Standardized mortality ratios, serving as the reference, were calculated on the basis of Minnesota White death rates.
During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (12.8%) had results greater than the upper limit of normal.
Of 6,823 patients with an ALT measurement, 911 (13%) had results higher than the upper limit of normal.
For AST, a level up to twice the upper limit of normal was associated with a 32% increase in the risk of death, and for more than twice that limit, the risk increased to 78% compared with the reference population.
Similarly, an ALT up to twice the upper limit of normal was associated with a 21% increase in the risk of death, and for more than twice that level, the risk increased to 59% versus the reference population.
In contrast, normal AST or ALT levels were associated with a mortality rate lower than expected (mortality rate 0.95 for AST and 0.61 for ALT).
After a median duration of 10.9 years, 4,639 individuals had died.
Of those who died, 73 (1.6%) died of liver disease including hepatobiliary malignancies (58.9% men), while 1,559 (33.6%) died of cardiovascular causes, 1,015 (21.9%) of other malignancies, and 42% died of other or undetermined causes.
AST was significantly higher among those who died of liver disorders, the researchers said.
Although the precise reasons for the association in this study are unclear, some individuals undoubtedly had elevated enzymes as a result of liver disease, the researchers said.
In addition, they suggested that aminotransferases, particularly ALT, might also be a marker for cardiovascular disease, via the metabolic syndrome, adding to the risk of death. Nearly 34% of the deaths in this study population were due to cardiovascular disease.
Also, they said, AST may become elevated in patients with acute myocardial injury or congestive heart failure.
Other conditions, such as chronic alcohol consumption and associated depression, substance abuse, smoking, and accidents may also have contributed to the mortality risk.
Limitations included the fact that the study individuals came from a routine medical care setting rather than a screening of random individuals in the community.
Only a minority of the community residents had their liver enzymes screened, and this study was based on a single aminotransferase result. Given the long lag-time between testing and death from liver disease, a study with longer follow-up might find a stronger association between the two.
Finally, the large proportion of whites in this study may reduce the generalizability of the data.
Although the findings presented here could not answer questions about routine prevention, measurement of these enzymes from a simple blood test may allow early detection and treatment of conditions that could lead to significant morbidity and mortality in the future, the investigators said.
This study was supported by grants from the National Institutes of Health. No potential conflicts of interest were reported.
Additional source: HepatologySource reference: Lee TH, et al "Serum aminotransferase activity and mortality risk in a United States community" Hepatology 2008; 47: 880-887.