Analysis of prognosis and background liver disease in non-advanced hepatocellular carcinoma in two decades

PLoS One. 2024 Mar 7;19(3):e0297882. doi: 10.1371/journal.pone.0297882. eCollection 2024.


Background/aim: Antiviral hepatitis and systemic therapies for hepatocellular carcinoma (HCC) remarkably progressed in the recent 10 years. This study aimed to reveal the actual transition and changes in the prognosis and background liver disease in non-advanced HCC in the past 20 years.

Methods: This retrospectively recruited 566 patients who were diagnosed with non-advanced HCC from February 2002 to February 2022. The prognosis was analyzed by subdividing according to the diagnosis date (period I: February 2002-April 2009 and period Ⅱ: May 2009-February 2022).

Results: Patients in period II (n = 351) were significantly older, with lower albumin-bilirubin (ALBI) scores and alpha-fetoprotein (AFP) and more anti-viral therapy, systemic therapy, and hepatic arterial infusion chemotherapy as compared with those in period I (n = 215). The etiology ratio of the background liver disease revealed decreased hepatitis C virus from 70.6% to 49.0% and increased non-B, non-C from 17.7% to 39.9% from periods I to Ⅱ. The multivariate analysis revealed older age and higher ALBI score in Barcelona Clinic Liver Cancer (BCLC) 0/A stage, AFP of >20 ng/mL, and higher ALBI score in BCLC B stage as independent prognosis factors. Fine-Gray competing risk model analysis revealed that liver-related deaths significantly decreased in period II as compared to period I, especially for BCLC stage 0/A (HR: 0.656; 95%CI: 0.442-0.972, P = 0.036).

Conclusion: The characteristics of patients with non-advanced HCC have changed over time. Appropriate background liver management led to better liver-related prognoses in BCLC 0/A.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Liver Neoplasms* / pathology
  • Prognosis
  • Retrospective Studies
  • alpha-Fetoproteins


  • alpha-Fetoproteins

Grants and funding

This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Numbers 23fk0210106, 23fk0210104, 23fk0210113, 23fk0210102, 23fk0310501, 22ama221302, 23fk0210118, 23fk0210126, 23fk0210123 and Grant-in-Aid for Scientific Research (KAKENHI grant numbers 22K20910, 22K08005, 21K15942, 21K07939, 21K07977, 21H02896, 21K19476, 22H03054, 23K15066). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.