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Adjuvant interferon (IFN) therapy following curative treatment for hepatocellular carcinoma (HCC) has been extensively investigated; however, the clinical benefits with different hepatitis backgrounds remain unclear. Medline, Embase, PubMed and the Cochrane Library databases were searched to identify randomized trials and cohort studies that enrolled HCC patients who received curative surgery or ablation therapy followed by IFN and control subjects; the studies were required to include data on early or late recurrence and mortality rates of HCC. Hepatitis B virus (HBV) associated with HCC (HBV-HCC) and hepatitis C virus (HCV) associated with HCC (HCV-HCC) were separately analyzed and recurrence, mortality and clinicopathological factors were compared. A total of 14 studies (9 randomized trials and 5 cohort studies, including 1,385 patients in total) were eligible for meta-analysis. IFN was found to decrease mortality and early recurrence rates, but exerted no effect on late recurrence rate. The effect of IFN differed between HBV-HCC and HCV-HCC cases. In HCV-HCC, IFN significantly reduced mortality as well as recurrence rates. However, in HBV-HCC patients, IFN reduced mortality rather than recurrence rates, although it also reduced the recurrence rate in certain subgroups. In conclusion, the effect of adjuvant IFN on postoperative recurrence differed between HBV-HCC and HCV-HCC cases; therefore, different strategies with adjuvant IFN should be used to treat HCC with different hepatitis backgrounds. [ABSTRACT FROM AUTHOR]