a-Fetoprotein (AFP) is a fetal serum protein (1,2), and its reappearance in mice with hepatoma was demonstrated by Abelev et al. (3) in 1963 and in patients with liver cancer by Tatarinov (4,5) nearly at the same time. The association of raised serum levels of AFP with yolk sac tumors was documented later by Abelev et al. (6) and Masopust et al. (7). Interestingly, Tatarinov (5, 8) suggested that AFP is a marker of hepatoma on the basis of results obtained with a very small number of patients with this disorder. This was probably possible because AFP is a highly specific and sensitive marker of hepatocellular carcinoma (HCC) as it was shown later by a number of workers. An AFP-positive case of fulminant hepatitis was also found in his early studies using an immunodiffusion technique, and the appearance of AFP in other hepatitis and cirrhosis was reported later in a collaborative study (9) using a similar test system. Development of a sensitive RIA system (10, 11) enabled us to study low levels of AFP in patients with benign liver diseases and malignant tumors of other origins.It is now generally accepted that a considerable number of patients with acute and chronic hepatitis and cirrhosis without malignancy show slight but significant elevations of serum AFP (11-14). Regulatory mechanisms of increased AFP synthesis in hepatic injury and in malignant transformation have been explored at the cellular and molecular levels (15-18). The recognition of raised serum levels of AFP is clinically important because AFP-positive patients with chronic hepatitis and cirrhosis have a high risk of liver-related death (19-20) or development of HCC (14, 21, 22). Currently, serum levels of AFP at the time of hepatoma diagnosis became lower as a result of the advent of advanced imaging and biopsy techniques in the diagnosis of HCC, resulting in a wider overlapping zone of AFP levels between benign and malignant liver diseases. Accordingly, it becomes more important to discriminate between AFP elevation associated with hepatoma evolution and that with hepatitis and cirrhosis alone. Thus the lectin-dependent fractionation of AFP originally described by Brqborowicz, Mackiewicz and Brqborowicz (23) and Miyazaki, Endo and Oda (24) is now an important complementary test in the follow-up of patients with chronic liver diseases. The present review will focus on these new developments in AFP research and their clinical application in hepatology. Other related areas of AFP research will be covered by recently published review articles (8, 13, 15, 22, 25-31).
MOLECULAR PROPERTIES AND
PHYSIOLOGICAL ROLESHuman AFP is a glycoprotein with an electrophoretic mobility between albumin and a,-globulin, and its primary structure has been determined from cDNA clones (32, 33). The number of amino acid residues in mature AFP is deduced from the nucleotide sequence of mRNA to be 590, and the molecular weight is calculated to be 69,063 with 4% carbohydrate. This figure agrees well with the generally accepted molecular weight of 72,000, which was approxima...