Recent developments in the first detection of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The main aetiological factor is hepatitis B virus (HBV) although the importance of hepatitis C virus (HCV) is growing. The most important tumour marker for HCC is alpha-fetoprotein (AFP). The common method of screening high risk patients by AFP and ultrasonography has been shown to result in earlier detection and consequently more easily treatable tumours and longer survival. Proposed screening interval varies from once every 3 months to annually to "as indicated' but, most commonly, is once every 6 months. AFP is a fairly specific but insensitive marker for HCC. Sensitivity of HCC detection by blood markers is improved by combining various other markers with AFP. Of the other markers, the newer high sensitivity des-gamma-carboxy-prothrombin (DCP) has been found to be useful. In addition the AFP fractions L3, P4/5 and the +II band are highly specific for HCC. Among routinely assayed tumour markers in the laboratory, CA 125 is more sensitive for HCC than AFP but far less specific. Various other enzymes, isoenzymes, growth factors, adhesion molecules, other proteins such as interleukin-2 receptor (IL-2R), human cervical cancer oncogene protein (HCCR) and glypican-3 (GPC3), p15 and p16 hypermethylation and nitrite/nitrate ratio have been tested; some of these show promise but none is presently in routine use. The value of other newer markers such as the HBx protein that is produced by HBV, and what are thought to be specific proteins and signatures identified by proteomics remain to be determined.

Figure 1

Receiver-operating characteristic (ROC) curves for AFP in HCC when compared to benign liver diseases (AFP: HCC-BLD) and all diseased controls (AFP: HCC-DC) Reproduced with permission, from reference .

Figure 2

Plot of Youden indices [(sensitivity + specificity) – 100], in percent, at various cut-offs, for AFP in HCC when compared with benign liver diseases (BLD) and all diseased controls (DC). Reproduced with permission, from reference .

Figure 3

ROC curves for various tumour markers in HCC, when compared with benign liver diseases. Reproduced with permission, from reference .