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

This version was published on 1 September 2009

Ann Clin Biochem 2009;46:377-384
© 2009 Association for Clinical Biochemistry


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Original Articles

Kazunori Miyake1,
Noriko Miyake1,
Shigemi Kondo1,
Yoko Tabe1,
Akimichi Ohsaka2 and
Takashi Miida1

1 Department of Clinical Laboratory Medicine;
2 Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan

Corresponding author: Kazunori Miyake MD. Email: cpm{at}

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

Methods: The ‘latent reference values’ of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase ({gamma}GT), cholinesterase (ChE)and total bilirubin (T-Bil) were extracted from a seven-yeardatabase of outpatients (aged 20–79 yr; comprising approximately1,270,000 test results). After calculating the monthly meansfor each variable, the time-series data were separated intotrend 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 periodicityand fluctuation range. A two-year outpatient database (215,000results) from another hospital was also analysed to confirmthe 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 {gamma}GT(in men). In contrast, T-Bil increased by 3.6% (men) and 5.0%(women) in the summer. The total protein and albumin concentrationsdid not change significantly. AST and ALT showed similar seasonalvariation 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 considerationwhen establishing either reference intervals or cut-off values,which are especially important regarding aminotransferases.

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