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Updated: Jun 21, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis
Natsuko Kawada1, Kazuho Imanaka, Tsukasa Kawaguchi
1Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
Purpose:
Characteristics of hepatocellular carcinoma (HCC) complicating nonalcoholic steatohepatitis (NASH) are still controversial. Most NASH related HCCs are believed to develop from cirrhotic liver, but case reports about HCC arising from non-cirrhotic NASH have been accumulating recently. This study is designed to elucidate characteristics of NASH related HCC diagnosed with high accuracy by using surgically resected specimens that contain larger areas to validate than biopsy specimens.
Methods:
For this study, 1168 patients who underwent hepatic resection at Osaka Medical Center for Cancer and Cardiovascular Diseases were enrolled. Patients who had clinically obvious causes of chronic liver dysfunction, such as viral and alcoholic hepatitis, were excluded. Histological diagnosis of NASH was confirmed according to Brunt's criterion.
Results:
Eight (1%) patients were diagnosed with NASH. Six (75%) of them showed non-cirrhosis in non-cancerous areas. Stages of fibrosis in the non-cirrhotic patients were mild fibrosis (F2) in five and moderate fibrosis (F3) in one. All patients complicated with metabolic diseases. Although all these patients without cirrhosis were evaluated pathologically at tumor-node-metastasis stages I or II, three (50%) had multiple recurrences of tumor within a short time after surgery.
Conclusion:
This study indicates HCC might arise frequently from non-cirrhotic NASH. While further studies are needed to confirm this observation, both cirrhotic and non-cirrhotic NASH warrant regular screening for HCC.
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