Background: The incidence of hepatitis B virus surface antigen-negative and hepatitis C virus antibody-negative hepatocellular carcinoma (NBNC-HCC) is gradually increasing. Methods: A retrospective cohort study was performed in 694 patients who underwent curative hepatic resection for primary HCC from January 1990 to December 2011. Results: In the NBNC-HCC group (n = 110), the complication rate of diabetic mellitus (38 %) was significantly higher than that of the B-HCC group (n = 110; 17 %), and their rate of alcohol abuse (38 %) was significantly higher than that of both the B-HCC (26 %) and C-HCC groups (n = 474; 22 %). In the NBNC-HCC group, the tumor diameter (4.5 ± 3.6 cm) was significantly larger than that of the C-HCC group (2.9 ± 1.8 cm), but the rate of histological cirrhosis (37 %) was significantly lower than those of both the B-HCC (67 %) and C-HCC (53 %) groups. There were no significant differences regarding overall and disease-free survival among the three groups. In the NBNC-HCC group, multiple intrahepatic or distant recurrences (25 %) were significantly higher than in the C-HCC group (17 %), and the rate of recurrence more than 2 years after hepatic resection (24 %) was significantly higher than that of the B-HCC group (12 %). Conclusions: The surgical outcomes of patients with NBNC-HCC were not significantly different compared with those of the patients with B-HCC or C-HCC. There was a substantial population with late recurrence among the patients with NBNC-HCC after curative hepatic resection, and thus not only long-term follow-up but also the early establishment of preventive methods for HCC recurrence from NBNC-hepatitis are necessary.
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