Background: The impact of viral factors on the prognosis of hepatocellular carcinoma (HCC) remains controversial because of heterogeneous populations included in previous reports. This study aims to compare clinicopathologic features and prognoses between patients with hepatitis B- and hepatitis C-related HCC who underwent resection surgery. Methods: We enrolled 609 patients with positive serum hepatitis B virus (HBV) surface antigen (HBsAg) and negative serum antibody against hepatitis C virus (anti-HCV) as the B-HCC group and 206 patients with negative serum HBsAg and positive anti-HCV as the C-HCC group. The overall survival rates and cumulative recurrence rates were compared between these two groups. Results: B-HCC patients were significantly younger, predominantly male, had better liver functional reserve, but more advanced tumor stage than C-HCC patients. After a median follow-up period of 40.6 months, 427 patients had died. Furthermore, 501 patients had tumor recurrence after surgery. The postoperative overall survival rates (p = 0.640) and recurrence rates (p = 0.387) of the two groups were comparable. However, the overall survival rate was higher in the B-HCC group than in the C-HCC group in the cases of transplantable HCC (p = 0.021) and Barcelona-Clinic Liver Cancer stage A HCC (p = 0.040). Conclusions: Viral etiologies were not apparent in determining outcomes of HCC patients who underwent resection due to heterogeneous studied populations. In early-stage HCC, B-HCC patients had better outcomes than C-HCC patients did because of better liver reserve and less hepatic inflammation.
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