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Updated: Jul 18, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Clinical characteristics of NonBNonC- HCC: Comparison with HBV and HCV related HCC
Kinuyo Hatanaka1, Masatoshi Kudo, Toyokazu Fukunaga
1Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
Objective:
To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC).
Methods:
A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics.
Results:
For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonBNonC-HCC in all HCC was 5-8% from 1991 to 1998, and has increased to 10-12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients.
Conclusion:
Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.
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