DOI 10.1515/cclm-2013-0096 Clin Chem Lab Med 2013; 51(10): 1997–2007 Anna Carobene*, Federica Braga, Thomas Roraas, Sverre Sandberg and William A. Bartlett A systematic review of data on biological variation for alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase Abstract Background: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) are enzymes measured in serum or plasma to investigate liver disease. The aim of this work is to assess the validity of published biological variation (BV) data currently avail- able for these enzymes. Methods: Publications containing BV data for ALT, AST and GGT were identified by searching PubMed using the following keywords: biological varia*, RCV, CV w , CV i , CV b , and CV g . The 95% confidence intervals for the within- and between-subject coefficients of variation were calculated using the analytical imprecision, the number of subjects, samples and replicates. Results: The searches identified 10 publications with ALT, 14 with AST and nine with GGT data. The protocols presented in those publications as used were varied. The ranges of within-subject variation reported were: ALT: 11.1%–58.1%, AST: 3.0%–32.3% and for GGT: 3.9%–14.5%. The median values (ALT: 18.0%, AST: 11.9% and GGT: 13.8%) were similar to those listed in a BV database com- monly used as a reference source. Conclusions: Published BV data for ALT, AST and GGT demonstrate a wide range of values derived from incon- sistent protocols. The quality of the presentations of the data is variable. These findings raise concerns around the utility of the data currently available and highlight the need for critical appraisal of such publications. The working group on BV of the European Federation of Clini- cal Chemistry and Laboratory Medicine is undertaking work to develop a critical appraisal checklist for the pro- duction and publication of reliable BV data. Keywords: biological variation; enzymes; quality specifi- cation; reference change value. *Corresponding author: Anna Carobene, Standardization Laboratory, Diagnostica e Ricerca San Raffaele S.p.A., via Olgettina 60, 20132 Milan, Italy, Phone: +39 2 26432850, Fax: +39 2 26434178, E-mail: carobene.anna@hsr.it Anna Carobene, Federica Braga and William A. Bartlett: European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), Working Group Biological Variation, www.efcclm.org Federica Braga: Chair of Clinical Biochemistry and Clinical Molecular Biology, University of Milan Medical School, Milan, Italy Thomas Roraas and Sverre Sandberg: Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Haraldsplass Hospital, Bergen, Norway Sverre Sandberg: Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway William A. Bartlett: Blood Sciences, Ninewells Hospital and Medical School Ninewells, Dundee, UK Introduction Alanine aminotransferase (ALT), aspartate aminotrans- ferase (AST) and γ-glutamyl transferase (GGT) measure- ments in serum or plasma are important for the iden- tification and monitoring of liver disease. Knowledge of biological variation (BV) of these enzymes not only enables assessment of the significance of changes in serial measurements observed within a subject [1], but also allows definition of analytical goals to enable safe appli- cation of laboratory measurements in a clinical setting [2]. In addition, BV data can be used to derive an index of individuality (II) to assess the utility of conventional pop- ulation-based reference intervals for these measurements [3]. Given the importance of BV data in these contexts it is clear that access to BV data is essential to the clinical laboratory and that users should be confident that they are well characterised and fit for purpose. There are compiled sources of BV data available to the laboratory medicine specialist. Fraser published a collec- tion of BV data (including data from 1988 through 1991) in 1992 [4]. In 1999 Ricos et al. [5] made available a data- base comprising of a collection of data including BV of biochemical and haematological analytes. That database of published data has since been expanded, updated and made available online [6]. It is now widely used and refer- enced as an important source of BV data for clinical appli- cation. Some limitations of this approach have, however, Brought to you by | University of Missouri-Columbia Authenticated | 128.206.9.138 Download Date | 9/30/13 9:20 PM