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    Establishing continuous reference intervals for liver function analytes using fractional polynomial regression
    (Walter De Gruyter Gmbh, 2025) Yildirim, Didem Derici; Fidanci, Senay Balci; Sengul, Merve Turkegun; Cimen, M. Burak Y.; Tamer, Lulufer
    Objectives Reference intervals (RIs) play a crucial role in contemporary healthcare by providing critical support for clinical decision-making. RI calculation methods have certain limitations. They cannot capture age-related variations in laboratory values and non-linear relations between variables. Therefore, alternative methods that preserve the continuous type of age and consider non-linear relations must be explored. This study aimed to suggest an alternative method, namely, fractional polynomial (FP) regression models, to overcome these limitations and estimate the reference limits based on this method for ALT and AST markers.Methods This retrospective study is conducted on a large hospital database to establish continuous age and sex-specific RIs for ALT and AST in a Turkish population. The study included 4,386 and 2,834 individuals for ALT and AST, respectively, aged 18-92 years. FP models and a non-parametric approach are used to calculate RIs.Results For AST in females, a linear model indicated the relationship between age and AST in females (p=0.673). However, more complex models (m0=4) were explored for female ALT values. After several comparisons, the FP3 model was chosen as the best fit (p=0.098). For male ALT and AST, FP analysis showed no significant age-related effects (p=0.679 and p=0.507, respectively). Therefore, traditional non-parametric methods were used to calculate RIs.Conclusions Compared with discrete RIs, continuous RIs are more accurate. Laboratories should determine RIs that reflect their population. Future research could explore the application of FP models in the pediatric population.