Antiplatelet Therapy Improves the Prognosis of Patients with Hepatocellular Carcinoma

Abstract

Aims: Antiplatelet therapy has been reported to reduce liver fibrosis and hepatocellular carcinoma (HCC), and has exhibited antitumor properties in other cancers. However, the effects of antiplatelet therapy after diagnosis of HCC are unknown. We investigated the effects of antiplatelet therapy on prognosis, tumor progression, liver function and safety in HCC patients.

Methods: We retrospectively analyzed 772 HCC patients. Antiplatelet therapy was defined as the regular intake of aspirin or clopidogrel from HCC diagnosis through to an endpoint of either overall survival (OS) or liver-related death. Overall survival, liver-related death, tumor progression, Child-Pugh deterioration and hemorrhage were analyzed for patients who either had or had not undertaken antiplatelet therapy.

Results: The numbers of patients who did and did not undertake antiplatelet therapy were 111 and 661, respectively. Patients who undertook antiplatelet therapy were older and had better liver function at diagnosis. Antiplatelet therapy resulted in significant improvements in OS (p < 0.01) and lower risk of liver-related death (p < 0.01). Multivariate Cox regression analysis revealed that antiplatelet therapy had a significant negative association with liver-related death (hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.44-0.93, p = 0.02). In patients who underwent transcatheter arterial chemoembolization (TACE) as the first treatment, antiplatelet therapy prevented tumor progression (p < 0.01) and Child-Pugh deterioration (p < 0.01). Antiplatelet therapy did not increase the risk of hemorrhagic events.

Conclusions: Antiplatelet therapy reduced liver-related death and improved OS safely in HCC patients.

Keywords: antiplatelet therapy; hepatocellular carcinoma; prognosis.

Figure 1

Overall survival and cumulative incidence of liver-related deaths in HCC patients who did or did not undertake antiplatelet therapy. (a) Five-year overall survival rates for antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 59.0% and 33.5%, respectively. Antiplatelet therapy resulted in significantly better prognoses (log-rank test; p < 0.001). (b) Five-year cumulative incidence rates of liver-related deaths with antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 36.1 and 62.4%, respectively. Antiplatelet therapy resulted in significantly better prognoses (log-rank test; p < 0.001).

Figure 2

Cumulative incidence of tumor progression stratified by first treatment method, i.e., curative therapy (a) and TACE (b). In curative therapy (a), antiplatelet therapy (dotted line) had no effect on HCC recurrence (p = 0.26), compared to no antiplatelet therapy (solid line). However, in TACE (b), antiplatelet therapy was associated with significantly longer times to tumor progression. Five-year cumulative incidence rates for antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 80.0% and 97.1%, respectively (p = 0.005).

Figure 3

Cumulative incidence of Child–Pugh deterioration stratified by first treatment methods, i.e., curative therapy (a) and TACE (b). In curative therapy, five-year cumulative incidence rates of antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 30.0% and 48.6%, respectively (p = 0.08). In TACE (b), five-year cumulative incidence rates of antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 59.6% and 82.4%, respectively (p < 0.001).

Figure 4

Cumulative incidence of hemorrhagic events in all patients. Five-year incidence rates for antiplatelet therapy (dotted line) and no antiplatelet therapy (solid line) were 23.1% and 21.4%, respectively (p = 0.33).