Establishment And Verification Of Reference Intervals For Commonly Used Liver Function Items In Healthy Children And Adolescents Aged 1~<18 Years In Jilin Province

Objective: As an important tool for clinical decision-making [1],reference interval(RI)refers to range between the low and high values of reference limits.Liver function items in healthy children and adolescents are essential for monitoring of growth and development in children and adolescents,reflecting youths' physical condition,diary,nutrient status and etc[5].Aim of this research is to explore reference intervals of commonly used liver function items of healthy children and adolescents aged 1~<18 years in Jilin Province,China,and to establish and verify suitable and practical reference intervals.Methods: According to document EP28-A3c[3] issued by the American Institute of Clinical and Laboratory Standards(CLSI)and the health industry standard WS/T 402-2012[4],well-maintained VITROS 5600 automatic biochemical analyzer and Dirui CS-1200 automatic biochemical analyzer were used for detection of 9 common liver function items: albumin(ALB),total protein(TP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),?-glutamyl transfer peptidase(GGT),alkaline phosphatase(ALP),total bilirubin(TBIL),direct bilirubin(DBIL),and unconjugated bilirubin(Bu)in this experiment.Reagents,quality control products and standard products were used by Ortho Clinical Diagnostics and Dirui respectively.A total of 6322 individuals(3119 males,3203 females)included in this study.As for data process,outliers were removed and normality were examined.Z test was applied for determination of gender and/or age partition.Nonparametric method,presented as 2.5–97.5 percentile ranges with 90 percentile confidence intervals,was performed for establishment of reference intervals.Scatter plot for determination of tendency of subjects in each subgroup.SPSS 21.0,Med Calc,LMS,EXCEL were used for statistical analysis and graphing.RIs were compared with national industry standards and other pediatric reference intervals from different countries.Established RIs were validated at 29 clinical laboratories of 9 different administrative districts across Jilin.Correlation between liver function items with gender and age as well as comparison of two systems were analyzed.Results: A total of 6322 healthy children and adolescents were enrolled in the study,including 3119 males and 3203 females,with gender ratio of 1:1.03.When establishing the RIs,TBIL,DBIL and Bu do not design the reference lower limit,only the reference upper limit,that is 95% of the measured value.All items showed significant difference among age groups,the same as situation between genders except TP.ALB,ALT,AST,GGT,ALP TBIL,DBIL,and Bu showed no gender difference in younger groups,as discrepancy occurred in older population.ALB,TP,GGT,TBIL,DBIL,and Bu levels increased with age while 1~<2 years old children appeared to have the highest ALT and AST levels.ALP inclined steadily in younger groups before its peak at 11~<12 years old,then descending rapidly to the lowest level at 17~<18 years old.A total of 29 clinical laboratories in 9 administrative districts of Jilin Province were selected,and most of them were verified and accepted fundamentally.RIs of commonly used liver function items of healthy children and adolescents aged 1~<18 years old established by dry chemistry method and conventional wet chemical systems were comparable with RIs proposed of China's industry standards and foreign data which applied the same detection systems.ALB,TP,ALT,AST,GGT,ALP,TBIL,DBIL and Bu were all strongly age-related.ALB,TP,ALT,AST,GGT and ALP were gender-related except TBIL,DBIL and Bu.Dry chemical system and the wet chemical system were in good correlation on ALB,ALT,AST,GGT,ALP and TBIL with correlation coefficients were all above 0.800.Conclusions: 1.RIs of commonly used liver function items of healthy children and adolescents are very different from those of healthy adults.It is quite necessary to establish pediatric intervals.2.RIs should be partitioned by gender and age.3.Serum ALB,TP,GGT,TBIL,DBIL and Bu increase with age.Serum ALT,ALP levels fluctuate and serum AST decrease with age.4.RIs of dry chemistry system and wet chemistry by 29 clinical laboratories in 9 administrative districts in Jilin Province are verified and accepted fundamentally.5.Though there is significant correlation between the two systems of most items,RIs should be established separately.