Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.
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.
Mazzaferro
Vincenzo
V
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
Romito
Raffaele
R
Schiavo
Marcello
M
Mariani
Luigi
L
Camerini
Tiziana
T
Bhoori
Sherrie
S
Capussotti
Lorenzo
L
Calise
Fulvio
F
Pellicci
Riccardo
R
Belli
Giulio
G
Tagger
Alessandro
A
Colombo
Massimo
M
Bonino
Ferruccio
F
Majno
Pietro
P
Llovet
Josep M
JM
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
D006512:Hepatitis B Core Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins