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Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis

Mazzaferro, Vincenzo
Romito, Raffaele
Schiavo, Marcello
Mariani, Luigi
Camerini, Tiziana
Bhoori, Sherrie
Capussotti, Lorenzo
Calise, Fulvio
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Published in Hepatology. 2006, vol. 44, no. 6, p. 1543-54
Abstract Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA-positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant 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. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-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 after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.
Keywords AdultAgedCarcinoma, Hepatocellular/pathology/prevention & control/secondaryComorbidityFemaleHepatectomyHepatitis B Core Antigens/analysisHepatitis B, Chronic/complicationsHepatitis C, Chronic/complications/drug therapy/surgeryHumansInterferon-alpha/therapeutic useLiver Cirrhosis/drug therapy/surgeryLiver Neoplasms/pathology/prevention & controlMaleMiddle AgedMultivariate AnalysisNeoplasm Recurrence, Local/prevention & controlRecombinant ProteinsRiskAlpha-Fetoproteins/analysis
PMID: 17133492
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Research group Hépatologie chirurgicale (327)
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MAZZAFERRO, Vincenzo et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. In: Hepatology, 2006, vol. 44, n° 6, p. 1543-54. doi: 10.1002/hep.21415 https://archive-ouverte.unige.ch/unige:37006

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Deposited on : 2014-05-30

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