¹Department of Medical Research and ²Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan

Clinical utilization of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma (HCC) at its earlier stage (small tumor) is often considered to be nonspecific. This is because of the fact that, at a cut-off level of 10-20 mg/L, the occurrence of hepatitis (BH) and cirrhosis (BLC) may often produce false-positive result during the course of diagnosing possible HCC. For this reason, an adjunct marker is sought by us for the purpose of improving the specificity of AFP for the diagnosis of small tumor HCC. First, a panel consisting of AFP and ferritin-to-iron ratio (FIR) was considered and its clinical efficacy was subsequently evaluated. In this study, serum iron, ferritin and AFP levels were simultaneously measured in various groups of subjects: Group A (n=54) with histologically proven HCC, group B (n=27) with BLC, group C (n=28) with BH and group D (n=112) comprising healthy matched controls without liver diseases (normal liver function tests; HBsAg negative). Using AFP>25mg/L as the cut-off level, AFP was found to be abnormally elevated in 72% (39/54), 52% (14/27) and 50% (14/28) of all samples of HCC, BLC and BH sera tested. Along this line, we found that 87% (47/54), 81% (22/27) and 82% (23/28) of HCC, BLC and BH sera tested had abnormally higher values than the normal controls. However, it is interesting to note that if one uses a FIR value of 20 as a cut-off level, only 7% (2/27) and 4% (1/28) of patients in BLC and BH had elevated values. In contrast 33% (17/54) of patients with HCC had abnormally higher FIR values. Furthermore, if both AFP (>25mg/L) and FIR (>20) were used as a dual marker, a further decrease in positivity rate of BLC (4%, 1/27) and BH (0%, 0/28) can be achieved. However, the positivity rate of HCC group remains unchanged (33%, 17/45). Our data suggest that a combined utilization of AFP and FIR can greatly improve the diagnostic specificity of AFP itself.