Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies

PLoS One. 2014 Mar 14;9(3):e91410. doi: 10.1371/journal.pone.0091410. eCollection 2014.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Population Surveillance*
  • Proportional Hazards Models
  • Publication Bias

Substances

  • Alanine Transaminase

Grants and funding

This work was supported in part by the National Nature Science Foundation of China (NSFC 81072321, 30760243, 30460143 and 30560133), 2009 Program for New Century Excellent Talents in University (NCET), Guangxi Nature Sciences Grant (GuiKeGong 1104003A-7), Guangxi Health Ministry Medicine Grant (Key-Scientific-Research-Grant Z201018), grants from Programs for Changjiang Scholars and Innovative Research Team in University (No. IRT1119) and Innovative Research Team in Guangxi Natural Science Foundation (No. 2011GXNSFF018005). No funding body had any influence or input into the study design, data collection, analysis, data interpretation, or writing of the report.