Problems of Long Survival Following Surgery in Patients with NonBNonC-HCC: Comparison with HBV and HCV Related-HCC

Background: The number of patients with hepatocellular carcinoma (HCC) in the absence of both hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) (NBNC-HCC) has been rapidly increasing in Japan. The objective of this study was to compare the clinical and pathological characteristics between patients with the NBNC-HCC, those with HBsAg positive HCC (B-related HCC) and HCVAb positive HCC (C-related HCC). A better understanding will facilitate the development of postoperative strategies to better manage patients with NBNC-HCC. Methods: Consecutive 219 patients with primary HCC: (B-related, n=35; C-related, n = 104; NBNC, n = 80) were treated by hepatic resection or ablation. Clinicopathological characteristics including postoperative course were retrospectively compared between the three groups. Results: When comparing within stage I and II, the NBNC-HCC group had improved recurrence free survival (RFS) compared to the C-related HCC (p = 0.013) but had not been good overall survival (OS). Moreover, the NBNC-HCC group showed higher rate of death due to other cancers and cardiovascular disease (p = 0.011) compared to the C-related HCC. Multivariate analysis revealed that the only prognostic factor for RFS in the NBNC-HCC group was high serum total bilirubin. Conclusions: In the patients with the NBNC-HCC, elevated serum bilirubin could predict poor RFS after surgery. Furthermore, patients must be carefully followed-up not only for HCC but also for the occurrence of other critical diseases including multiple other cancers.