Annual biological variation and personalized reference intervals of 8 serum liver enzymes and 3 noninvasive tests in fatty liver patients

Shuo Wang; Min Zhao; Zihan Su; Dan Yang; Runqing Mu

doi:10.1016/j.cca.2025.120156

Annual biological variation and personalized reference intervals of 8 serum liver enzymes and 3 noninvasive tests in fatty liver patients

Clin Chim Acta. 2025 Jan 25:569:120156. doi: 10.1016/j.cca.2025.120156. Online ahead of print.

Authors

Shuo Wang¹, Min Zhao¹, Zihan Su¹, Dan Yang¹, Runqing Mu²

Affiliations

¹ National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001 China.
² National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001 China. Electronic address: runqingmu@163.com.

PMID: 39870293
DOI: 10.1016/j.cca.2025.120156

Abstract

Background: The liver function tests and noninvasive tests (NITs) play important roles in the follow-up and monitoring of fatty liver disease (FLD). Our aim is to establish annual biological variation (BV) and personalized reference intervals (prRIs) of liver function tests for the first time in order to accurately assess the status and progress of FLD.

Methods: 67 fatty liver patients who participated in regular physical examination once a year for six consecutive years, were enrolled. Based on these patients, we calculated annual BV and derived parameters, including reference change value (RCV), index of individuality (II), and total variation around the true homeostatic set point (TV_set) which could further be used to derive prRI.

Results: We calculated the annual within-subject BV (CV_I), within-person BV (CV_P), RCV, II, TV_set of 8 liver function tests and 3 NITs for fatty liver patients. CV_I estimates of fatty liver patients for half of liver function tests were significantly lower than those of healthy people and these could lead to a lower RCV. IIs of all measurands were < 1.4 except for total bile acids (TBA). The mean of CV_P is similar to the CV_I; however, there is a significant heterogeneity in CV_P among different subjects. Annual TV_set estimates for 7 measurands were lower and prRI was also narrower in fatty liver patients than that of healthy people.

Conclusion: Annual BV and their derived parameters based on fatty liver patients can provide an objective basis for the monitoring and follow-up of FLD, a global epidemic disease.

Keywords: Biological variation; Fatty liver disease; Index of individuality; Personalized reference intervals; Reference change value.