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The association of low serum alanine aminotransferase activity with mortality in the US population.

ABSTRACT: Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988-1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of persons in deciles 4-9 (mortality was relatively flat across these deciles) over an 18-year period (through 2006) among 14,950 viral-hepatitis-negative adults. In NHANES 1999-2006, low ALT was evaluated in association with dual-energy x-ray absorptiometry body composition measures among 15,028 adults. Multivariate-adjusted mortality was higher for decile 1 (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.24, 1.63), decile 2 (HR = 1.27, 95% CI: 1.06, 1.53), and decile 3 (HR = 1.25, 95% CI: 1.04, 1.50) and nonsignificantly higher for decile 10 (HR = 1.21, 95% CI: 0.91, 1.61) than for deciles 4-9. Adjusted appendicular lean mass was decreased among the lowest ALT deciles. In the US population, low ALT was associated with higher mortality risk, possibly attributable to decreased appendicular lean mass. For mortality studies of elevated ALT levels, the most appropriate comparison group is persons in the middle range of ALT rather than all persons with nonelevated ALT.

SUBMITTER: Ruhl CE

PROVIDER: S-EPMC3858105 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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The association of low serum alanine aminotransferase activity with mortality in the US population.

Ruhl Constance E CE Everhart James E JE

American journal of epidemiology 20130926 12

Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988-1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of p ...[more]

PMID: 24071009

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Project description:OBJECTIVE: Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. METHODS: Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/? 70 years). RESULTS: A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23-1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88-0.94), 0.91 (0.85-0.96), 0.92 (0.86-0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). CONCLUSIONS: The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in predicting mortality in the older population; extremely low ALT levels indicated a higher all-cause, CV-related, and cancer-related mortality. ALT activity may therefore be a useful biomarker when predicting the long-term survival of elderly patients.

Project description:BackgroundThe aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio has been shown to be associated with poor clinical outcomes across various patient groups. However, little is unclear about the association between the two in critically ill older patients. Therefore, we aim to investigate the association of the AST/ALT ratio with hospital mortality in this special population.MethodsIn this retrospective cohort study, we extracted elderly patients (age ≥ 65 years) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was in-hospital mortality. The association between the AST/ALT ratio and hospital mortality was studied using univariable and multivariable Cox regression analysis, as well as restricted cubic splines (RCS). Survival analysis was performed using the Kaplan-Meier (KM) method according to the AST/ALT ratio.ResultsAmong the 13,358 eligible patients, the mean age was 77.6 years, 7,077 patients (52.9%) were male, and 2,511 patients (18.8%) died in hospital. The AST/ALT ratio was found to be independently associated with in-hospital mortality (HR = 1.05, 95% CI: 1.01-1.09, P = 0.022) after adjusting for potential confounders. Furthermore, a non-linear relationship and saturation effect were observed between them, with the inflection point being 1.80. When the AST/ALT ratio was less than 1.80, we found that every 1 unit increase in the AST/ALT ratio resulted in a 39% increased risk of in-hospital mortality (HR = 1.39, 95% CI: 1.18-1.64, P < 0.001). However, when the AST/ALT ratio was greater than 1.80, the association became saturated (HR = 1.01, 95% CI: 0.96-1.07, P = 0.609). Sensitivity and subgroup analyses showed the results were robust.ConclusionIn critically ill older patients, the association between the AST/ALT ratio and in-hospital mortality was non-linear and showed a saturation effect. An elevated AST/ALT ratio was significantly associated with increased in-hospital mortality when the AST/ALT ratio was less than 1.80.

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The association of low serum alanine aminotransferase activity with mortality in the US population.

Publications

The association of low serum alanine aminotransferase activity with mortality in the US population.

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