Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhoticpatients

OBJECTIVES: High hepatocyte proliferation has been recently proposed as a r isk factor for the development of hepatocellular carcinoma (HCC). The aim o f this study was to assess whether hepatocyte proliferation is an independe nt risk factor for HCC when considered together with clinical and demograph ic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histol ogical diagnosis of cirrhosis and preserved liver function, enrolled in a s urveillance program for early diagnosis of HCC. Hepatocyte proliferation wa s evaluated by flow-cytometric analysis in liver samples collected at the t ime of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha -fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12-120 months), 12 pa tients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5% +/- 1.6 in patients who developed HCC and 0.9% +/- 0.6 in those who did not (I, < 0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables sig nificantly correlated with the development of HCC (I, < 0.0001, p < 0.0001) . Multivariate analysis found that both variables were independently associ ated with HCC development (p < 0.003 and p < 0.005, respectively), with haz ard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Am ong patients with high AFP and/or high S-phase fraction, ii (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AF P, corresponding to HCC yearly incidences of 9.5% and 0.3% (p < 0.00009). CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surv eillance program. (C) 2001 by Am. Cell. of Gastroenterology.