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) 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-α (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.