BackgroundThe incidence of non-hepatitis B virus, non-hepatitis C virus hepatocellular carcinoma (non-B non-C-HCC) is increasing worldwide. We assessed the clinical characteristics and surgical outcomes of non-B non-C-HCC, versus hepatitis B (HBV-HCC) and hepatitis C (HCV-HCC).MethodsEtiologies, fibrosis stages, and survival outcomes were analyzed of 789 consecutive patients who underwent surgery from 1990 to 2020 (HBV-HCC,n= 149; HCV-HCC,n= 424; non-B non-C-HCC,n= 216).ResultsThe incidence of hypertension and diabetes mellitus was significantly higher in patients with NON-B NON-C-HCC than in those with HBV-HCC and HCV-HCC. Significantly more advanced tumor stages were observed in patients with non-B non-C-HCC; however, better liver function and lower fibrosis stages were observed. Patients with non-B non-C-HCC had significantly worse 5-year overall survival than patients with HBV-HCC; overall survival was comparable between patients with non-B non-C-HCC and HCV-HCC. Patients with HCV-HCC had significantly worse 5-year recurrence-free survival than patients with HBV-HCC and non-B non-C-HCC. In patients with non-B non-C-HCC, overall survival was comparable among three periods (1990–2000, 2001–2010, and 2011–2020) despite significant improvement in patients with HBV-HCC and HCV-HCC.ConclusionThe prognosis of non-B non-C-HCC was similar to that of HBV-HCC and HCV-HCC regardless of tumor progression at surgery. Patients with hypertension, diabetes mellitus, and dyslipidemia require careful systematic follow-up and treatment.