Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma

Abstract

Aim: To assess whether a 24-wk course of interferon (IFN) could prevent hepatocellular carcinoma (HCC) recurrence and worsening of liver function in patients with hepatitis C virus (HCV)-infected patients after receiving curative treatment for primary HCC.

Methods: Outcomes in 42 patients with HCV infection treated with IFN-alpha, after curative treatment for primary HCC (IFN group), were compared with 42 matched curatively treated historical controls not given IFN (non-IFN group).

Results: Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%, 44%, 61%, and 67% vs 4.8%, 53%, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively), IFN group showed a lower rate than the non-IFN group for second recurrence (0%, 10.4%, 28%, and 35% vs 0%, 30%, 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively). Among the IFN group, patients with sustained virologic response (SVR) were less likely to have a second HCC recurrence than IFN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival.

Conclusion: Most intrahepatic recurrences of HCV-related HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival.

Figure 1

Cumulative recurrence rates after curative treatment of HCC. A: Rates of first recurrence compared between IFN and non-IFN groups, showed no significant difference (P = 0.153); B: Rates of second recurrence compared between IFN and non-IFN groups. The second recurrence rate for the IFN group was lower than that for the non-IFN group (P = 0.022).

Figure 2

Cumulative recurrence rates according to SVR to IFN therapy after curative treatment of HCC. A: Rates of first recurrence compared among SVR, non-SVR and non-IFN groups. The rate of first recurrence of HCC in the SVR group was significantly lower than in the non-SVR and non-IFN groups (P = 0.002, P = 0.016, respectively). No significant difference in first recurrence rate was seen between the non-SVR and non-IFN groups (P = 0.381); B: Rates of second recurrence compared among the three groups. Second recurrence of HCC was suppressed in the SVR group compared with the non-SVR and non-IFN groups (P = 0.0037, P = 0.0019, respectively), and to a more pronounced degree than for the first recurrence rate. No significant difference in second recurrence rate was seen between the non-SVR and non-IFN groups (P = 0.90).

Figure 3

Cumulative survival rates after curative treatment of HCC. A: Comparison of cumulative survival rates in the IFN and non-IFN groups. The cumulative survival rate was significantly higher in the IFN group than in the non-IFN group (P = 0.039); B: Comparison of cumulative survival rates in the SVR, non-SVR and non-IFN groups. Although no significant overall difference was found between the SVR and non-SVR groups (P = 0.538), the SVR group had a particularly high survival rate compared with the non-IFN group (P = 0.029).

Figure 4

Influence of IFN therapy after curative treatment of HCC on Child-Pugh scores. IFN-treated patients were less likely to show deterioration of hepatic function. In particular, liver function scores in the SVR group were significantly better preserved than in the non-IFN group (P = 0.003). Median observation time was 59.8 mo in the SVR group, 45 mo in the non-SVR group, and 51.8 mo in the non-IFN group.