Rapid Communication
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2007; 13(37): 5009-5014
Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.5009
Liver angiogenesis as a risk factor for hepatocellular carcinoma development in hepatitis C virus cirrhotic patients
Roberto Mazzanti, Luca Messerini, Camilla E Comin, Lorenzo Fedeli, Nathalie Gannè-Carrie, Michel Beaugrand
Roberto Mazzanti, Lorenzo Fedeli, Dipartimento di Medicina Interna, Sezione di Oncologia Medica, Centro di Eccellenza DENOthe Azienda Ospedaliero-Universitaria Careggi, Istituto Toscano Tumori, Università degli Studi di Firenze, Florence, Italy
Luca Messerini, Camilla E Comin, Dipartimento di Patologia Umana ed Oncologia, Istituto Toscano Tumori, Università degli Studi di Firenze, Florence, Italy
Nathalie Gannè-Carrie, Michel Beaugrand, Service d’Hepato-Gastroenterologie, Hopital Jean Verdier, Assistance Publique-Hopitaux de Paris et UFR SMBH-Universite Paris XIII, Bondy, France
Author contributions: All authors contributed equally to the work.
Supported by Grants from the Italian Ministry of University, Scientific and Technological Research (MIUR, Progetto Nazionale cofinanziato COFIN No. 2002067115), and the University of Florence to R. M.
Correspondence to: Professor Roberto Mazzanti, MD, Department of Internal Medicine, University of Florence School of Medicine, Viale GB Morgagni 85, I-50134 Firenze, Italy. r.mazzanti@dmi.unifi.it
Telephone: +39-55-4296471 Fax: +39-55-4296468
Received: April 4, 2007
Revised: July 16, 2007
Accepted: July 26, 2007
Published online: October 7, 2007
Abstract

AIM: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients.

METHODS: One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.

RESULTS: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (χ2 = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: χ2 = 1.41; P = 0.2351; PCNA: χ2 = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD ≤ 4 (P = 0.0006). No relationship was found between MIB1 or PCNA and MVD (MIB-1 r2 = 0.00007116, P = 0.9281; PCNA: r2 = 0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk.

CONCLUSION: Liver angiogenesis has a role for in HCV-related liver carcinogenesis and for defining patients at higher risk.

Keywords: Liver cancer, Hepatitis C virus, Angiogenesis, Proliferating cell nuclear antigen