INCREASED RISK OF HEPATOCELLULAR-CARCINOMA DEVELOPMENT IN PATIENTS WITH CIRRHOSIS AND WITH HIGH HEPATOCELLULAR PROLIFERATION

The immunohistochemical determination of the accessory protein of DNA- polymerase delta (PCNA), a marker of an early S-phase of the cell cycl e, was used to evaluate cell proliferation retrospectively in formalin -fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. P roliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO ) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA po sitivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually develop ed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed b y a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cho lesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provide d no further information. From these data, hepatocellular proliferatio n can be evaluated in patients with cirrhosis with a currently availab le technique. Patients with high cell proliferation are at increased r isk of developing hepatocellular carcinoma and may require differentia ted follow up. (C) Journal of Hepatology.