HONOLULU — Measurement of the L3 glycoform of serum α-fetoprotein provides a unique early warning of the presence of hepatocellular carcinoma in patients at high risk due to chronic liver disease, Dr. Young Y. Wang reported at the annual meeting of the American College of Gastroenterology.
Indeed, the ratio of serum α-fetoprotein (AFP)-L3 to total AFP provides a substantial improvement in predictive power for this purpose over the conventional use of total AFP. This conclusion was reached on the basis of findings from a seven-center, double-blind, prospective comparative study involving 440 patients at high risk for hepatocellular carcinoma (HCC) because of liver cirrhosis and/or chronic hepatitis, according to Dr. Wang of Wako Pure Chemical Industries Ltd., Richmond, Va.
An assay that determines the AFP-L3/total AFP ratio using an automated analyzer—the Wako liquid-phase binding assay system, or LiBASys—gained Food and Drug Administration approval last July as a risk assessment test in patients at elevated risk for HCC, the fourth most common type of cancer and the No. 3 cause of cancer mortality worldwide.
Of the 440 patients, 39 were diagnosed with HCC using generally accepted criteria during the multiyear Wako-sponsored study. Patients with an elevated AFP-L3/total AFP ratio of 10% or more had a 40% chance of developing radiologically confirmed HCC within the next 21 months. Follow-up lasted about 2.5 years.
This translated into an 8.2-fold increased relative risk of HCC, compared with that in patients with a ratio of less than 10%. An elevated ratio had 51% sensitivity and 93% specificity for the detection of HCC.
In contrast, a total AFP above the cutoff point of 10 ng/mL was associated with only a 5.3-fold increased relative risk, along with 80% sensitivity and 62% specificity. A total AFP above the alternative threshold of 100 ng/mL conferred a 4.1-fold increased relative risk of HCC with 26% sensitivity and 94% specificity.
The mean time between development of an elevated AFP-L3/total AFP ratio and radiologic evidence of HCC was 205 days. A positive assay warrants stepped-up evaluation for the malignancy, Dr. Wang suggested.
The reason total serum AFP has proved suboptimal for early detection of HCC is that it consists of three glycoforms. AFP-L1 is generated mainly by inflammatory cells in the liver, hence this AFP subfraction is elevated in patients with chronic liver disease without HCC. AFP-L2 comes from testicular carcinoma and other germ cell tumors. AFP-L3 is the glycoform generated by malignant hepatocytes.