Department of Nutritional Carcinogenesis, IRCCS S. de Bellis National Institute for Digestive Diseases, Castellana Grotte, Italy.
Background: Hepatocellular carcinoma (HCC) size at diagnosis is important in management. Without screening programs, tumor size at diagnosis is heterogeneous. Aims: To examine the clinical parameters related to tumor size. Methods: Using prospectively collected data from a 1,100-patient biopsy-proven HCC cohort presenting in the absence of screening, tumor sizes were ordered and trichotomized and the resulting terciles were compared for tumor and blood parameters. Results: The terciles were significantly different with respect to portal hypertension and thrombocytopenia, which were present in a higher percent of tercile I patients with smaller tumors. Tercile III patients with larger HCCs had the highest serum α-fetoprotein (AFP), γ-glutamyl transpeptidase (GGTP), and alkaline phosphatase (ALKP) levels and the most portal vein (PV) thrombosis. Subclassification of tercile I patients by AFP showed that patients with high serum AFP had increased numbers of tumor nodules, more PV thrombosis, higher bilirubin, ALKP, and GGTP levels, and shorter survival. Conclusions: Smaller-tumor tercile I patients had more advanced portal hypertension with thrombocytopenia than did larger-tumor patients. Tercile I patients with higher AFP levels had more frequent PV thrombosis and worse survival than those with lower AFP levels. Elevated serum GGTP and ALKP levels appear to be associated with a more aggressive HCC phenotype. These differing patterns suggest more than one HCC pathway.