Seasonal variation in liver function tests: a time-series analysis of outpatient data

Ann Clin Biochem. 2009 Sep;46(Pt 5):377-84. doi: 10.1258/acb.2009.008203. Epub 2009 Jul 29.


Background: Long-term physiological variations, such as seasonal variations, affect the screening efficiency at medical checkups. This study examined the seasonal variation in liver function tests using recently described data-mining methods.

Methods: The 'latent reference values' of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (gammaGT), cholinesterase (ChE) and total bilirubin (T-Bil) were extracted from a seven-year database of outpatients (aged 20-79 yr; comprising approximately 1,270,000 test results). After calculating the monthly means for each variable, the time-series data were separated into trend and seasonal components using a local regression model (Loess method). Then, a cosine function model (cosinor method) was applied to the seasonal component to determine the periodicity and fluctuation range. A two-year outpatient database (215,000 results) from another hospital was also analysed to confirm the reproducibility of these methods.

Results: The serum levels of test results tended to increase in the winter. The increase in AST and ALT was about 6% in men and women, and was greater than that in ChE, ALP (in men and women) and gammaGT (in men). In contrast, T-Bil increased by 3.6% (men) and 5.0% (women) in the summer. The total protein and albumin concentrations did not change significantly. AST and ALT showed similar seasonal variation in both institutions in the comparative analysis.

Conclusions: The liver function tests were observed to show seasonal variations. These seasonal variations should therefore be taken into consideration when establishing either reference intervals or cut-off values, which are especially important regarding aminotransferases.

MeSH terms

  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Cholinesterases / blood
  • Female
  • Humans
  • Liver Function Tests / standards*
  • Male
  • Middle Aged
  • Seasons*
  • Sex Factors
  • gamma-Glutamyltransferase / blood


  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Cholinesterases