Early Fibrosis but Late Tumor Stage and Worse Outcomes in Hepatocellular Carcinoma Patients Without Hepatitis B or Hepatitis C


Background and Aims

The features of non-viral, nonalcohol hepatocellular carcinoma (NBNC-HCC) remain elusive. The aim of this study was to investigate this clinical characteristics and overall survival of NBNC-HCC compared to hepatitis B- (HBV-HCC) and hepatitis C-related (HCV-HCC) HCC.


We analyzed the etiologies, fibrosis stages, clinical data, and outcomes of newly diagnosed patients with HCC.


A total of 1777 HCC patients were recruited, including 332 patients with NBNC-HCC, 682 patients with HBV-HCC, 680 patients with HCV-HCC, and 83 patients with HBV/HCV HCC. Patients with NBNC-HCC were older (69.9 ± 11.9 years). Patients with NBNC-HCC exhibited a higher prevalence of diabetes (43.9%) compared to the HBV-HCC (27.1%, p < 0.05) and HCV-HCC (30.2%, p < 0.05) groups. Compared to patients from the viral-related HCC groups, patients with NBNC-HCC exhibited a significantly lower fibrosis stage. NBNC-HCC patients exhibited a higher proportion of Barcelona Clinic Liver Cancer (BCLC) classification stage C and stage D compared to patients from the HBV-HCC and HCV-HCC groups. With a mean of 2.33 ± 2.31 years of follow-up, the median survival of patients with NBNC-HCC was 1.75 (95% CI 1.33–2.17) years, which was significantly lower than that of patients with HBV-HCC (p = 0.041) and HCV-HCC (p < 0.001).


Patients with NBNC-HCC have a higher risk of diabetes than patients with HCC of viral etiologies. Although patients with NBNC-HCC exhibited a milder fibrosis stage, their more advanced HCC stages and worse overall survival should be taken into consideration in clinical care.

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This study was supported partly by grants from The Ministry of Science and Technology, Taiwan (MOST104-2314-B-037-078-MY3, 107-2314-B-037-082-MY3), and Kaohsiung Medical University Hospital (S10606, S10709, KMUH106-6R07). The authors thank secretary help from Taiwan Liver Research Foundation (TLRF). The foundation did not influence how the study was conducted or the approval of the manuscript. The authors also thank Dr. Tyng-Yuan Jang and Dr. Ta-Ya Lin for their active contribution in revising the manuscript.

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Correspondence to Jee-Fu Huang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Institutional Review Board of Kaohsiung Medical University Chung-Ho Memorial Hospital (IRB Number: KMUHIRB-E(II)-20180281) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Hsu, PY., Hsu, CT., Yeh, ML. et al. Early Fibrosis but Late Tumor Stage and Worse Outcomes in Hepatocellular Carcinoma Patients Without Hepatitis B or Hepatitis C. Dig Dis Sci 65, 2120–2129 (2020). https://doi.org/10.1007/s10620-019-05938-3

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  • Hepatocellular carcinoma
  • Liver fibrosis
  • Cancer staging
  • Nonalcoholic fatty liver disease