title: High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity.
abstract: The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5% (mean, 2.1%), being significantly higher in the 50 patients who developed HCC during 88 +/- 42 months of follow-up than in the 158 patients who remained cancer-free (3.6% +/- 2.4% vs. 1.6% +/- 1.5%; P <.0001). By receiver operating curve (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and low risk for developing cancer. By multivariate analysis, high histologic grading scores and gender were associated to PCNA LI >2.0%. The yearly incidence of HCC was 5.2% for the 80 patients with PCNA-LI >2.0% compared with 1.1% for the 128 with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate analysis, PCNA-LI >2.0% was the strongest independent predictor of cancer (hazard ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in patients with high liver cell proliferative activity rates than in those with low proliferative rates (10% vs. 75%; P <.0001). In conclusion, development of HCC in patients with compensated cirrhosis seems to be reliably predicted by liver cell proliferation status.
authors.affiliation: Division of Hepatology, IRCCS Maggiore Hospital, Milan, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Donato
authors.forename: E
authors.initials: E
authors.lastname: Arosio
authors.forename: E
authors.initials: E
authors.lastname: Del Ninno
authors.forename: G
authors.initials: G
authors.lastname: Ronchi
authors.forename: P
authors.initials: P
authors.lastname: Lampertico
authors.forename: A
authors.initials: A
authors.lastname: Morabito
authors.forename: M R
authors.initials: MR
authors.lastname: Balestrieri
authors.forename: M
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism; D002455:Cell Division; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D018809:Proliferating Cell Nuclear Antigen