Serum levels of alphafetoprotein are raised in 60-80% of patients with
hepatocellular carcinoma. Although widely used as a
serum marker, frequent false-positive results in patients with benign
liver disease, result in poor specificity. This occurs particularly when levels of alphafetoprotein fall between 50-500 ng ml-1, the so-called 'grey area'. Recent reports suggest that isoelectric focusing of alphafetoprotein demonstrates certain bands that are more specific for
hepatocellular carcinoma. Our aim was to determine whether the apparent specificity of this new approach is gained at the expense of decreased sensitivity. Sera from 110 patients with a 'non-diagnostic' serum alphafetoprotein level (50-500 ng ml-1) were examined by isoelectric focusing and quantified by densitometric scanning. Ten patients with chronic
liver disease and a raised serum alphafetoprotein level (50-500 ng ml-1), but with no evidence of
hepatocellular carcinoma, were also studied. Isoelectric focusing revealed characteristic
hepatocellular carcinoma bands (bands +II and +III) in 96% patients overall, and 100% of those with levels of total alphafetoprotein greater than 100 ng ml-1. No such bands were seen among ten subjects with
cirrhosis but without
hepatocellular carcinoma. Bands that are characteristic of
hepatocellular carcinoma (bands +II or +III) are seen in the great majority of
hepatocellular carcinoma patients; their absence makes a diagnosis of
hepatocellular carcinoma extremely unlikely.