Reference interval with age-gender variation for 4 liver function parameters in an adult segment of the Indian population

Objectives: The proper interpretation of the laboratory values seen in individuals depends on the validity of the reference intervals. These intervals may differ from one population to another due to variation in factors such as genetic profile, physical characteristics, and dietary intake. Reference intervals for most parameters are not available for the Indian population. This study presents reference intervals for 4 liver function parameters: total protein, albumin, globulin, and the albumin-globulin ratio for a segment of the Indian population, as well as a study of age trend and gender differences. Methods: The results were based on a minimum of 12.264 values for each parameter from individuals aged 0 to 98 years. These values were extracted from a large database of the laboratory of a tertiary care hospital after careful filtration of the appropriate reference values. The age-gender variation in the mean and median was examined and the reference intervals were obtained as 2.5th to 97.5th percentile. Results: There was a sufficient number of values in the various age groups and by gender except for the group aged 0-14 years. Therefore, this age group was excluded. The age trend was studied for males and females separately, as gender differences were substantial and consistent across age groups. Total protein and albumin levels declined with age, but the decline in albumin level was more rapid. Specific age-gender reference intervals were obtained for adults. Conclusion: The effect of age and gender on all of the parameters examined was substantial. The obtained reference intervals are slightly different from those previously reported in the literature and currently used.


1. Furruqh S, Anitha D, Venkatesh T. Estimation of reference values in liver function test in health plan individuals of an urban south Indian population. Indian J Clin Biochem 2004;19(2):72–9.

2. Malati T. Whether western normative laboratory values used for clinical diagnosis are applicable to Indian population? An overview on reference interval. Indian J Clin Biochem 2009;24(2):111–22.

3. Clinical and Laboratory Standard Institute. EP 28- A3C Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guidelines – Third Edition. CLSI, 2010:p2.Available at: sample.pdf. Accessed Apr 7, 2020.

4. Andersen IB, Brasen CL, Christensen H, Noehr-Jensen L, Nielsen DE, Brandslund I, et al. Standardised Resting Time Prior to Blood Sampling and Diurnal Variation Associated with Risk of Patient Misclassification: Results from Selected Biochemical Components. PLoS One 2015;10(10):e0140475.

5. Chambers C. The registered reports revolution: Lessons in cultural reform. Significance 2019;16(4):23–7.

6. Indrayan A, Bhargava M, Shukla S. Utilization of hospital data for establishing normal reference interval of quantitative medical parameters: Double filtration method. Indian J Med Biochem (Accepted).

7. Indrayan A, Holt MP. Concise Encyclopedia of Biostatistics for Medical Professionals. Chapman & Hall /CRC Press; 2018.

8. Wasserstein RL, Schirm AL. Lazar NA. Moving to a world beyond “p<0.05”. American Statistician 2019;73:1–19.

9. Indrayan A, Malhotra RK. Medical Biostatistics. 4th ed. CRC Press; 2018.

10. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006;7(2):79–108.

11. Tarran B. The S word… and what to do about it. Significance 2019;16(4):14.

12. Telo S. Kaman D. Measurement uncertainty in biochemical parameters. Medicine Science Int Med Jour 2018. Available at: cae78b2193f881ec6b3418e0920.pdf. Accessed Apr 7, 2020.

13. Milinković N, Ignjatović S, Šumarac Z, Majkić-Singh N. Uncertainty of Measurement in Laboratory Medicine. J Med Biochem 2018;37(3):279–88.

14. Burtis CA, Bruns DE. Tietz Fundamentals of Clinical Chemistry and Medical Diagnostics. 7th ed. Elsevier; 2015.

15. Sairam S, Domalapalli S, Muthu S, Swaminathan J, Ramesh VA, Sekhar L, et al. Hematological and biochemical parameters in apparently healthy Indian population: defining reference intervals. Indian J Clin Biochem 2014;29(3):290–7.

16. Ashavaid TF, Todur SP, Dherai AJ. Establishment of reference intervals in Indian population. Indian J Clin Biochem 2005;20(2):110–8.

17. Weaving G, Batstone GF, Jones RG. Age and sex variation in serum albumin concentration: an observational study. Ann Clin Biochem 2016;53(Pt 1):106–11.

18. ScienceDaily. Genetic basis for gender differences in the liver. Available at: Accessed Apr 7, 2020.

19. Ozarda Y, Ichihaa K, Aslan D, Aybek H, Ari Z, Taneli F, et al. A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers. Clin Chem Lab Med 2014;52:1–11.

20. Cieslak KP, Bennink RJ, de Graaf W, van Lienden KP, Besselink MG, Busch OR, et al. Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection. HPB (Oxford) 2016;18(9):773–80.

21. Kim IH, Kisseleva T, Brenner DA. Aging and liver disease. Curr Opin Gastroenterol 2015;31(3):184–91.

22. Pathology Harmony Group. Harmonisation of reference intervals. Available at: committees/scientific/guidelines/acb/pathology-harmony-iibiochemistry.pdf?sfvrsn=2. Accessed Apr 7, 2020.

Kaynak Göster