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

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 (TVset) which could further be used to derive prRI. Results: We calculated the annual within-subject BV (CVI), within-person BV (CVP), RCV, II, TVset of 8 liver function tests and 3 NITs for fatty liver patients. CVI 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 CVP is similar to the CVI; however, there is a significant heterogeneity in CVP among different subjects. Annual TVset 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.