Background/Aims: To clarify risk factors and clinical features of both hepatitis B surface antigen and anti-HCV negative hepatocellular carcinoma (NBNC-HCC). Methods: HCC patients (n = 1,109) diagnosed at a single center were categorized based on the presence of serum hepatitis B surface antigen and HCVAb. Clinical characteristics of 127 NBNC-HCC patients were evaluated. Results: NBNC-HCC patients were stratified as those with alcoholic liver disease (ALD-HCC, n = 42) and alcohol-unrelated liver disease (non-ALD-HCC, n = 85). Compared with the ALD-HCC group, the non-ALD-HCC group had a higher prevalence of diabetes (p = 0.015), larger tumor size (p = 0.007), and higher tumor marker levels (p = 0.014). Liver function results were significantly worse in ALD-HCC than in non-ALD-HCC. Although the ALD-HCC group had a higher tendency toward recurrence than the non-ALD-HCC group, survival rates were similar between groups (p = 0.352). Conclusion: Alcohol consumption was the most common etiologic factor for NBNC-HCC, and diabetes may be related to the development of HCC in non-ALD-HCC patients. Non-ALD-HCC tended to be diagnosed at a more advanced stage, whereas liver function was worse, and tumor recurrence rate was higher in ALD-HCC patients. Further examination of the risk factors and establishment of a precise surveillance system are necessary for early diagnosis and the development of curative therapies for NBNC-HCC.

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