title: Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.
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.
authors.affiliation: Department of Surgery, Biomedical Statistics, Pathology, National Cancer Institute of Milan and Chair of Gastroenterology, Policlinico Foundation, Department of Medicine, University of Milan, Italy. vincenzo.mazzaferro@istitutotumori.mi.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Raffaele
authors.initials: R
authors.lastname: Romito
authors.forename: Marcello
authors.initials: M
authors.lastname: Schiavo
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Tiziana
authors.initials: T
authors.lastname: Camerini
authors.forename: Sherrie
authors.initials: S
authors.lastname: Bhoori
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Fulvio
authors.initials: F
authors.lastname: Calise
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellicci
authors.forename: Giulio
authors.initials: G
authors.lastname: Belli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tagger
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
authors.forename: Pietro
authors.initials: P
authors.lastname: Majno
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llovet
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D015897:Comorbidity; D005260:Female; D006498:Hepatectomy; D006512:Hepatitis B Core Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000601:surgery; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011994:Recombinant Proteins; D012306:Risk; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D006512:Hepatitis B Core Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins