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

Abstract

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 (gGT), 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 gGT (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.

The Genetic Architecture of Liver Enzyme Levels: GGT, ALT and AST

“…The seasonal effects were similar to those found in a large Japanese study (based on almost 300,000 liver function test results). While ALT and AST levels showed seasonal variation, showing peak values in the winter and a nadir in the summer, GGT did not (Miyake et al 2009). In future research, it will be of interest to further examine the mechanism that underlies this annual variation in liver enzyme levels.…”

Serum bilirubin levels in familial hypercholesterolemia: a new risk marker for cardiovascular disease?

“…Because current smoking would not accurately refl ect previous exposure to smoking, we have chosen not to include this variable in the multiple regression analyses. Seasonal variation in bilirubin could also be an infl uence ( 28 ); however, subjects were recruited for the study throughout the whole year, so we assume that this phenomenon played a minor role. Finally, the association between CVD and bilirubin could possibly be confounded by patients with concomitant elevated liver enzymes ( 5,10 ).…”

Effect of Seasonal Variation on Adult Clinical Laboratory Parameters in Rwanda, Zambia, and Uganda: Implications for HIV Biomedical Prevention Trials

“…Direct bilirubin concentrations were higher in the rainy compared to the dry season at Lusaka and Masaka but contrary results were obtained at Kigali. Total bilirubin has been reported to increase in the summer in other settings [37]. Mean ALT concentrations were higher in the rainy compared to the dry season at Kigali and Lusaka but remained unchanged at Masaka.…”

“…Mean ALT concentrations were higher in the rainy compared to the dry season at Kigali and Lusaka but remained unchanged at Masaka. Seasonal variation of ALT may be attributed to seasonal changes in vascular tone, climatic stress, hormones, and alcohol intake [37].…”