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

✍ Scribed by Vincenzo Mazzaferro; Raffaele Romito; Marcello Schiavo; Luigi Mariani; Tiziana Camerini; Sherrie Bhoori; Lorenzo Capussotti; Fulvio Calise; Riccardo Pellicci; Giulio Belli; Alessandro Tagger; Massimo Colombo; Ferruccio Bonino; Pietro Majno; Josep M. Llovet

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 563 KB
• Volume: 44
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21415

✦ Synopsis

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-␣ (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. (HEPATOLOGY 2006;44:1543-1554.