Antiplatelet Therapy is Associated with a Better Prognosis for Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma after Liver Resection

Ann Surg Oncol. 2016 Dec;23(Suppl 5):874-883. doi: 10.1245/s10434-016-5520-9. Epub 2016 Aug 19.

Abstract

Background: Recurrence of hepatocellular carcinoma (HCC) with unsatisfactory survival is common after surgical resection. Antiplatelet therapy with aspirin or clopidogrel was recently shown to prevent hepatic carcinogenesis in a murine model, but its effect in humans had not been clarified. This study aimed to investigate the association between antiplatelet therapy and the outcomes for patients with hepatitis B virus (HBV)-related HCC after liver resection.

Methods: By analyzing data from the Taiwan National Health Insurance Research Database, 9461 HBV-related HCC patients who had undergone liver resection between January 1997 and December 2011 were identified. After one-to-four matching by sex, age, and propensity score, 442 patients with antiplatelet therapy and 1768 patients without antiplatelet therapy were enrolled for the analysis. The Kaplan-Meier method and modified Cox proportional hazards models were used for survival and multivariable, stratified analyses.

Results: Recurrence-free survival and overall survival after resection surgery were significantly better after 5 years in the treated cohort than in the untreated cohort (52.8 vs 47.9 %; p = 0.021 and 80.3 vs 65.4 %; p < 0.001, respectively). Besides, antiplatelet therapy reduced the risk of HCC recurrence (hazard ratio [HR] 0.73; p < 0.001) and overall mortality (HR 0.57; p < 0.001) in the multivariable analysis. However, antiplatelet use significantly increased the risk of upper gastrointestinal bleeding (odds ratio [OR] 1.91; p < 0.001).

Conclusions: Use of aspirin or clopidogrel was associated with better recurrence-free survival and overall survival among patients with HBV-related HCC after liver resection. However, these agents should be used with caution due to the adverse effects of upper gastrointestinal bleeding.

MeSH terms

  • Adult
  • Aged
  • Aspirin / therapeutic use
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology
  • Clopidogrel
  • Disease-Free Survival
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology*
  • Hepatectomy
  • Hepatitis B, Chronic / complications
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / surgery
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Proportional Hazards Models
  • Risk Factors
  • Survival Rate
  • Taiwan / epidemiology
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin