AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,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 anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther 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 withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(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 resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.Azzaroli F,Accogli E,Nigro G,Trerè D,Giovanelli S,MiracoloA,Lodato F,Montagnani M,Tamé M,Colecchia A,Mwangemi C,Festi D,Roda E,Derenzini M,Mazzella G.Interferon plusribavirin and interferon alone in preventing hepatocellularcarcinoma:A prospective study on patients with HCV relatedcirrhosis.World J Gastroenterol 2004;10(21):3099-3102http://www.wjgnet.com/1007-9327/10/3099.asp AIM: To determine the role of interferon (IFN) with or with tribavirin 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 HCVrelated liver cirrhosis plus compatible biochemistry andultasography were enrolled in the study. Biochemistry and ultrasonography were performed every 6 months. Ultrasoundguided liver biopsy was performed on all detected focalles. Froh-up lasted for 5 years. Cellular proliferation, evaluated by measuring Ag-NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index (AgNOR-PI) males, 14 females) were only followed up after the end of any treatment with IFN-alpha2b (old treatment controlgroup = OTCG). Sixty naive patients were stratified according to sex and AgNOR-PI an d then randomized in two groups: 30 were treated with IFN-alpha2b + ribavirin (treatmentgroup = TG), the remaining were not treated (control group = CG) .Nonresponders (NR) or relapsers in the TG receivedfurther IFN / ribavirin treatments after a HPO 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 HCCduring follow-up. The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG andCG (P <0.004) and between TG and CG (P <0.003) .CONCLUSION: IFN / ribavirin treatment associated with re-treatment courses of NR results to produce the best results in terms of HCC prevention. AgNOR-PI is a useful marker of possible HCC development. Azzaroli F, Accogli E, Nigro G, Trerè D, Giovanelli S, Miracolo A, Lodato F, Montagnani M, Tamé M, Colecchia A, Mwangemi C, Festi D, Roda E, Derenzini M, Mazzella G. Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: A prospective study on patients with HCV related cirrhosis. World J Gastroenterol 2004; 10 (21): 3099-3102http: //www.wjgnet.com/1007-9327/10/3099.asp