Resubclassification and clinical management for Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma

Chih Wen Lin, Yaw Sen Chen, Gin Ho Lo, Tsung Chin Wu, Jen Hao Yeh, Ming Lun Yeh, Chia Yen Dai, Jee Fu Huang, Wan Long Chuang, Lewis Roberts, Dae Won Jun, Hidenori Toyoda, Satoshi Yasuda, Mindie H. Nguyen, Ming Lung Yu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy. Methods: We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460). Results: In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child–Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2–53.7), 20.6 months (CI 14.1–25.9), 11.5 months (CI 8.02–14.1), 5.7 months (CI 4.02–5.98), and 3.2 months (CI 2.41–3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0–C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy. Conclusion: Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.

Original languageEnglish (US)
Pages (from-to)946-956
Number of pages11
JournalHepatology International
Issue number4
StatePublished - Aug 2021


  • Advanced stage
  • Hepatocellular carcinoma
  • Immunotherapy
  • Overall survival
  • Predictive factors
  • Prognosis
  • Substage
  • Surgical resection
  • Target therapy
  • Treatment

ASJC Scopus subject areas

  • Hepatology


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