Natural history of advanced hepatocellular carcinoma in Crete. Association with hepatitis C virus

Abstract

To investigate the clinical characteristics of advanced hepatocellular carcinoma (HCC) in Crete and to analyse the natural course of the untreated disease. Seventy-three patients (62 men) were enrolled in a prospective 4-year study. Clinical and virological parameters were recorded. Diagnosis was based on either ultrasound guided liver biopsy or a pathognomonic increase in alpha-fetoprotein plus compatible imaging. Statistical analysis was performed using histograms, contingency tables and one-way analyses of variance to analyse the characteristics of the disease. For survival analysis Kaplan-Meier survival curves and Cox's proportional hazards models were constructed. HCC in Crete is a mostly male disease (7:1 male:female ratio) and unlike in mainland Greece, it is mostly a hepatitis C virus (HCV)-related disease (54% HCV positive as opposed to only 13% in mainland Greece). Prognosis was associated with Okuda classification (Okuda stage III patients have a relative risk of dying that is seven to nine times higher than for Okuda stage I), the presence or absence of hepatitis B e antigen (HBeAg) and antibody to hepatitis B core antigen (anti-HBc). By contrast the presence of anti-HCV was not associated with a worse prognosis. A unit increase of albumin concentration was associated with an 11% decrease in the hazard rate. In general, Crete, despite the extremely similar population to the rest of Greece, resembles more closely the situation in Spain or Italy rather than mainland Greece.