Early and late recurrence of surgically resected hepatitis B virus-related hepatocellular carcinoma on nucleos(t)ide analogues therapy

J Formos Med Assoc. 2021 Aug;120(8):1563-1571. doi: 10.1016/j.jfma.2020.11.019. Epub 2020 Dec 15.

Abstract

Background/purpose: Hepatocellular carcinoma (HCC) is a highly recurrent tumor. Antiviral therapy with nucleos(t)ide analogues (NUCs) may reduce the risk of recurrence in hepatitis B virus (HBV)-related HCC. The risk factors associated with recurrence in HCC patients after surgical resection and with NUCs treatment should be delineated.

Methods: Consecutive 339 HBV-related HCC patients receiving surgical resection of HCC with NUCs therapy (including 256 entecavir, 36 tenofovir, and 18 lamivudine) after the surgery were retrospectively reviewed. Factors related to the recurrence-free survival (RFS) and overall survival (OS) were evaluated.

Results: After a median of 48.5 months of follow-up, 183 (54%) patients developed HCC recurrence, with the 5-year RFS of 42.8% and OS of 79%. Male gender (HR = 1.736, p = 0.037), baseline HBsAg level >200 IU/ml (HR = 1.748, p = 0.008), platelet count ≦100 (109/L) (HR = 1.592, p = 0.023), presence of microscopic vascular invasion (MVI) (HR = 1.499, p = 0.026), safety cut margin of ≦0.5 cm (HR = 1.507, p = 0.013), and Ishak fibrosis score 5-6 (HR = 1.579, p = 0.009) were independent factors associated with RFS in multivariate analysis. While tumor burden, platelet count, MVI, and safety cut margin were factors associated with early recurrence; baseline HBsAg level, and platelet count were independent factors associated with late recurrence. Ishak fibrosis score 5-6, poor differentiation, MVI, diabetes mellitus were factors associated with OS in multivariate analysis.

Conclusion: For HBV-HCC patients on NUCs treatment, tumor factors are associated with early recurrence, while HBsAg level and thrombocytopenia determines late recurrence. For patient with a high baseline HBsAg level, warning of higher risk of recurrence is required even under NUCs treatment.

Keywords: Early recurrence; Hepatitis B surface antigen; Hepatocellular carcinoma; Late recurrence; Nucleos(t)ide analogues.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / surgery
  • Hepatitis B Surface Antigens
  • Hepatitis B virus
  • Hepatitis B* / complications
  • Hepatitis B* / drug therapy
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / surgery
  • Male
  • Neoplasm Recurrence, Local
  • Retrospective Studies

Substances

  • Antiviral Agents
  • Hepatitis B Surface Antigens