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Tumor recurrence after resection ofhepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2years) as metastases or de novo tumors. Interferon (IFN) has the potential forchemoprevention against hepatitis C virus (HCV)-related cirrhosis. Apredetermined group of 150 HCV RNA-positive patients undergoing resection ofearly- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis Banticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV)(anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3times every week for 48 weeks [n = 76]) versus control (n = 74). The primaryend point was recurrence-free survival (RFS); secondary end points weredisease-specific and overall survival. Intention-to-treat and subgroup analysison adherent patients were conducted. Treatment effects on early/laterecurrences were assessed using multiple Cox regression analysis. No patientexperienced life-threatening adverse events. There were 28 adherent patients(37%). After 45 months of median follow-up, overall survival was 58.5%, and nosignificant difference in RFS was detectable between the two study arms (24.3%vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls),with a 50% reduction in late recurrence rate in the treatment arm. HCCmultiplicity and vascular invasion were significantly related to recurrence (P= .01 and .0003). After viral status stratification, while no treatment effectwas apparent in the mixed HCV+HBV population and on early recurrences (72events), there was a significant benefit on late recurrences (28 events) inHCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09-0.9; P = .04).In conclusion, IFN does not affect overall prevention of HCC recurrence afterresection, but it may reduce late recurrence in HCV-pure patients receivingeffective treatment. Leggil'articolo