Adjuvant interferon therapy after curative therapy for hepatocellular carcinoma (HCC): a meta-regression approach.

Background & Aims: Adjuvant anti-viral therapy after curative therapy for HCC has been studied extensively but the true clinical benefit and the predictors of efficacy remain unclear.

Methods: MEDLINE, PubMed, and the Cochrane library were searched until December 2008, plus the meeting abstracts of the American Association for the Study of Liver Disease 2005-2008. Randomized trials and cohort studies were included if the studies (1) enrolled HCC patients who had underlying chronic viral hepatitis B or C and had undergone curative surgery or ablation therapy; (2) consisted of one or more treatment arms with interferon-based therapy and a control arm of no anti-viral therapy; and (3) included recurrence-free survival of HCC as an endpoint. Meta-analysis and meta-regression were done according to the Cochrane guidelines.

Results: Thirteen studies (9 randomized trials and 4 cohort studies, totally 1180 patients) were eligible for meta-analysis. Surgery and ablation therapy were used in 9 and 8 studies, respectively. All studies used conventional interferon (natural or recombinant) as anti-viral therapy. Overall, interferon improved the 1-year, 2-year, and 3-year recurrence-free survival by 7.8% (95% CI 3.7-11.8%), 35.4% (95% CI 30.7-40.0%), and 14.0% (95% CI 8.6-19.4%), respectively (all p<0.01). Lower percentage of patients with multiple tumors and use of ablation therapy were independent predictors for better treatment efficacy.

Conclusion: The quantitative estimation of treatment efficacy and the identification of predictive factors in this study will help design future clinical trials of adjuvant therapy for HCC.