Alpha-fetoprotein-L3: Useful or Useless for Hepatocellular Carcinoma?

Japan is the only country where alpha-fetoprotein (AFP)-L3 can be measured in the routine clinical setting. Since AFP-L3 examination has been covered by health insurance in Japan for over 10 years, it is now routinely measured during general medical checkups for patients with chronic liver disease. To increase the specificity of AFP, the AFP-L3 glycoform can be used as a measure of cancerous changes in the AFP composite carbohydrate moiety. The most frequently used cut-off value is 10% [1], which gives a positive rate of 0/71 (0.0%), 1/90 (1.1%), 0/13 (0.0%), 0/14 (0.0%), and 18/82 (22.0%) for chronic hepatitis, hepatic cirrhosis, dysplastic nodules, early hepatocellular carcinoma, and advanced hepatocellular carcinoma, respectively. This yields a sensitivity of 18.8% and a specificity of 99.4%. Therefore, although AFP-L3 has high specificity, due to its low sensitivity, it is considered to be of limited use in screening. It is possible, however, to diagnose a marginally higher number of patients with advanced hepatocellular carcinoma [2]. Furthermore, as AFP-L3 may be elevated during hepatic failure, interpretation should be made with caution. AFP-L3 dynamics are largely related to the degree of biological malignancy of hepatocellular carcinoma [2, 3]. Results of pathological investigations conducted on patients who have undergone hepatic resection showed that those with infiltrative growth, capsular invasion, septum formation, portal vein infiltration, and hepatic vein infiltration were significantly more likely to have AFP-L3-positive (>10%) cancer [4]. To investigate cases of hepatocellular carcinoma for which therapeutic intervention was given and in which tumor markers were measured chronologically, an investigation was conducted prior to therapeutic intervention with a group of 196 AFP-L3-positive (>10%) patients and a group of 645 AFP-L3-negative patients. When the overall survival rate was compared between the AFP-L3-positive and negative groups, the latter group showed more favorable survival than the former group (p < 0.001). When the AFP-L3 dynamics before and at six months after treatment were compared, 599 cases remained negative, 113 remained positive, 83 underwent conversion from positive to negative (negative conversion), and 46 underwent conversion from negative to positive (positive conversion). When survival rates were investigated, the constantly negative and negative conversion groups had more favorable survival rates than the constantly positive and positive conversion group. In other words, even though there are AFP-L3-positive cancers with poor prognosis and a © 2013 S. Karger AG, Basel 2235-1795/13/0024-0151$38.00/0 www.karger.com/lic Liver Cancer 2013;2:151–152