Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 1, 2004; 10(21): 3099-3102
Published online Nov 1, 2004. doi: 10.3748/wjg.v10.i21.3099
Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: A prospective study on patients with HCV related cirrhosis
Azzaroli Francesco, Accogli Esterita, Nigro Giovanni, Trerè Davide, Giovanelli Silvia, Miracolo Anna, Lodato Francesca, Montagnani Marco, Tamé Mariarosa, Colecchia Antonio, Mwangemi Constance, Festi Davide, Roda Enrico, Derenzini Massimo, Mazzella Giuseppe
Azzaroli Francesco, Accogli Esterita, Nigro Giovanni, Giovanelli Silvia, Miracolo Anna, Lodato Francesca, Montagnani Marco, Tamé Mariarosa, Colecchia Antonio, Mwangemi Constance, Festi Davide, Roda Enrico, Mazzella Giuseppe, Department of Internal Medicine and Gastroenterology, University of Bologna
Trerè Davide, Derenzini Massimo, Department of Experimental Pathology, University of Bologna
Author contributions: All authors contributed equally to the work.
Correspondence to: Azzaroli Francesco, M.D., Department of Internal Medicine and Gastroenterology, S.Orsola Hospital (Pad. 5), University of Bologna Via Massarenti 9, 40138 Bologna. azzaroli@med.unibo.it
Telephone: +39-338-5316190 Fax: +39-51-6363316
Received: November 4, 2003
Revised: March 29, 2004
Accepted: April 6, 2004
Published online: November 1, 2004
Abstract

AIM: To determine the role of interferon (IFN) with or without ribavirin in preventing or delaying hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV) related cirrhosis. Data on the preventive effect of IFN plus ribavirin treatment are lacking.

METHODS: A total of 101 patients (62 males and 39 females, mean age 55.1 ± 1.4 years) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study. Biochemistry and ultrasonography were performed every 6 mo. Ultrasound guided liver biopsy was performed on all detected focal lesions. Follow-up lasted for 5 years. Cellular proliferation, evaluated by measuring Ag-NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index (AgNOR-PI) (cut-off = 2.5). Forty-one patients (27 males, 14 females) were only followed up after the end of an yearly treatment with IFN-alpha2b (old treatment control group = OTCG). Sixty naive patients were stratified according to sex and AgNOR-PI and then randomized in two groups: 30 were treated with IFN-alpha2b + ribavirin (treatment group = TG), the remaining were not treated (control group = CG). Nonresponders (NR) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal.

RESULTS: AgNOR-PI was significantly lowered by IFN (P < 0.001). HCC incidence was higher in patients with AgNOR-PI > 2.5 (26% vs 3%, P < 0.01). Two NR in the OTCG, none in the TG and 9 patients in the CG developed HCC during follow-up. The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG (P < 0.004) and between TG and CG (P < 0.003).

CONCLUSION: IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention. AgNOR-PI is a useful marker of possible HCC development.

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