Fib-4: analytical and biological issues

Fib-4 is a simple calculation based on the patient’s age and measurements of platelets, AST and ALT. It is recommended in some clinical guidelines to assist with evaluation of the risk of hepatic fibrosis. As with any laboratory result, understanding of the analytical and biological variation of the components is required. Using median within-laboratory precision data (CVa) from the RCPAQAP the estimated CVa for the FIB-4 result is 5.7%. Using data from the RCPAQAP Liquid Serum Chemistry program the total CVa for the whole country (within and between laboratory) is approximately 10%. The within subject biological variation (CVi) was estimated from the CVi of the input tests using data from the EFLM database, giving a result of approximately 14%. Estimation from laboratory data gave a CVi result of approximately 13%. To these sources of variation must be added other factors such as possible pyridoxine depletion, where susceptible assays are used, and interfering conditions (e.g., acute hepatitis, muscle damage, thrombocytopaenia from other causes). These findings suggest that decisions should not be based on a single estimation, and that patients should optimally be tested at one laboratory/with one method when using serial measurements. Laboratories could assist by supplying informative interpretative comments.