Reference Change Value for α-Fetoprotein and Its Application in Early Detection of Hepatocellular Carcinoma in Patients with Hepatic Disease

Hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide, with an incidence of 150 cases per 100 000 inhabitants per year in Asia and Africa and ∼5 cases per 100 000 per year in Europe, North America, and Australia (1). HCC can occur in healthy livers, but it is generally associated with hepatic disease. Cirrhosis is the most important risk factor for its development (2). Many studies have been dedicated to the early detection of HCC in patients with chronic liver disease (CLD), based on semiannual or annual measurement of serum α-fetoprotein (AFP) and ultrasound study of the liver. The interpretation of AFP results usually involves comparison with a fixed cutoff ranging from 20 to 500 μg/L, with sensitivities ranging from 33% to 64% (3)(4)(5). Another approach would be to assess changes in consecutive results from the same patient. To establish a criterion for dynamic assessment of a specific biological constituent, the first step is to define when a difference between two consecutive results indicates a change in a patient’s health status. The most widely accepted approach for this purpose is the so-called reference change value (RCV), a concept described by Harris and Brown (6). Using serial analytic results from the same individual for a specific constituent, it is possible to calculate the RCV that defines how large a difference between two consecutive determinations is statistically significant ( P <0.05). The RCV encompasses both biological and analytical variation. The RCV has been determined for various constituents in healthy persons and in some pathologies (7)(8)(9)(10)(11)(12)(13). In diseases that can modify the homeostatic set point and the degree of fluctuation of a specific constituent, the within-subject biological variation (BV) may be different …