Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies

PLoS One. 2024 Mar 15;19(3):e0290523. doi: 10.1371/journal.pone.0290523. eCollection 2024.


Background: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue.

Materials and methods: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder.

Results: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1).

Conclusion: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

MeSH terms

  • Carcinoma, Hepatocellular* / etiology
  • Carcinoma, Hepatocellular* / therapy
  • Hepacivirus
  • Hepatitis B virus
  • Hepatitis B*
  • Hepatitis C* / complications
  • Humans
  • Liver Neoplasms* / pathology
  • alpha-Fetoproteins


  • alpha-Fetoproteins

Grants and funding

• Initials of the authors who received each award: YHY • Grant numbers awarded to each author: CMRPG8N1131 • The full name of each funder: Kaohsiung Chang Gung Memorial Hospital • URL of each funder website: https://cghdpt.cgmh.org.tw/branch/shk • the funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.