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Clin Chem. 2017 Jun;63(6):1141-1150. doi: 10.1373/clinchem.2016.269811. Epub 2017 Apr 20.

Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum.

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Servizio Medicina di Laboratorio, Ospedale San Raffaele, Milan, Italy;
Biological Variation Working Group, European Federation of Clinical Chemistry and Laboratory Medicine, Milan, Italy (,
Norwegian Quality Improvement of Primary Health Care Laboratories (Noklus), Haraldsplass, Hospital, Bergen, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
Servizio Medicina di Laboratorio, Ospedale San Raffaele, Milan, Italy.
Certe, Wilhelmina Ziekenhuis Assen, Assen, the Netherlands.
Blood Sciences, Ninewells Hospital & Medical School, Scotland, UK.
Hospital Universitario La Paz, Madrid, Spain, and Quality Analytical Commission of the Spanish Society of Clinical Chemistry, Barcelona, Spain.
Department of Laboratory Medicine, University Hospital, Padua, Italy.
Acibadem University, School of Medicine, Atasehir, Istanbul, Turkey.



We sought to develop estimates of biological variation (BV) for 9 enzymes in blood serum as part of the European Biological Variation Study.


Ninety-one healthy study participants (38 male and 53 female, 21-69 years old) were phlebotomized in each of 10 consecutive weeks at 6 European laboratories. The same preanalytical sample-handling protocol was followed at each center before transport to San Raffaele Hospital, Milan, Italy, for analysis. Sera were stored at -80 °C before analysis in duplicate within a single run on an ADVIA 2400 Clinical Chemistry System (Siemens Healthcare) following a protocol designed to minimize analytical imprecision. Assay traceability was established using frozen sera with target values assigned by reference methods. The results were subjected to outlier analysis before CV-ANOVA to deliver valid BV estimates. Results for 9 enzymes were subsequently partitioned for graphical display allowing visual assessment of the effects of country of origin, sex, and age on BV estimates.


We found no effect of country upon the observed variation, but overall sex-related differences were evident for alanine amino transferase (ALT), γ-glutamyl transferase (GGT), and creatine kinase (CK). The following estimates for within-subject BV (CVI) and between-subject BV (CVG), respectively, were obtained: ALT: 9.3%, 28.2%; aspartate aminotransferase: 9.5%, 20.3%; GGT: 8.9%, 41.7%; alkaline phosphatase : 5.3%, 24.9%; lactate dehydrogenase: 5.2%, 12.6%; CK: 14.5%, 31.5%; amylase: 6.8%, 30.4%; pancreatic α-amylase: 6.3%, 24.9%; and lipase (LIP): 7.7%, 23.8%.


All CVI and some CVG estimates were lower than those reported in the online BV 2014 updated database. Analytical performance specifications derived from BV can be applied internationally.

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