Efficacy of interferon therapy in patients with hepatitis B virus-related primary hepatic carcinoma after transcatheter arterial chemoembolization

Abstract

Objective: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). There are few reports of adjuvant interferon (IFN) therapy for HBV-related HCC after TACE. The aim of the present study was to evaluate the effect of IFN therapy in patients with HBV-related primary HCC after TACE. Methods: The study included 138 patients with HBV-related unresectable HCC recruited from May 2014 to October 2015. Patients were randomly assigned to the control (n = 68, TACE) or observation group (n = 70, TACE + IFN), and were followed up for more than 24 months. Clinical indexes (cellular immune function, hepatic function, HBV DNA levels, hepatitis B e-antigen seroconversion and conversion rate, and hepatic fibrosis) before and after treatment, as well as the short-term curative effect and recurrence, were compared between the groups. To assess the effect of treatment based on the Modified Response Evaluation Criteria in Solid Tumors, progression-free survival, overall survival, and adverse events were recorded and compared. Results: After treatment, the percentages of CD3+, CD4+, CD4+/CD8+, and natural killer cells were significantly increased in the observation group (TACE + IFN group; P < 0.001) and significantly decreased in the control group (TACE group; P < 0.001). After 4 weeks, the levels of these cells in the observation group were significantly higher than in the control group (P < 0.001). Alanine aminotransferase improved significantly during the follow-up period in both the control and observation groups (P < 0.001), but was significantly lower in the observation group at 24 and 48 weeks (P < 0.001). At 48 weeks, the HBV DNA undetectable rate was 59.8% in the observation group, whereas HBV DNA levels increased after treatment in the control group; in fact, in 14 patients, HBV DNA levels increased >10-fold compared with baseline, and the activation rate was 20.6%. There was a significant difference in HBV DNA levels after treatment between the groups (P < 0.001). In the observation group, the hepatitis B e-antigen seroconversion rate was 45.0%, and the hepatitis B e-antigen conversion rate was 35.0%; there was no hepatitis B e-antigen seroconversion or conversion in the control group (χ2 = 9.258, P = 0.001). Hyaluronidase, the layer of mucin, type III collagen, and type IV peptide were decreased in the observation group (P < 0.05), and increased in the control group, and the difference between the groups was statistically significant (P < 0.05). There were statistically significant differences in both the disease control rate and objective response rate between the two groups (χ2 = 4.199, P = 0.040 and χ2 = 9.932, P = 0.001, respectively). At 24-month follow up, compared with the rates in the control group, the intrahepatic tumor recurrence rate (55.7% vs 69.1%, χ2 = 4.503, P = 0.034) and death rate (38.6% vs 64.7%, χ2 = 9.431, P = 0.002) in the observation group were significantly lower. Both the median progression-free survival (23.6, 95% [CI 21.4–25.8] months vs 20.3 [95% CI 15.8–24.8] months, χ2 = 4.58, P = 0.026) and overall survival (29.0 [95% CI 27.5–32.1] months vs 26.0 [95% CI 20.1–31.9] months, χ2 = 8.96, P = 0.003] were significantly longer in the observation group than in the control group. Multivariate analysis showed that the number of tumor nodules (P = 0.012) and TACE-IFN treatment (P = 0.008) were independent factors for overall survival. Conclusions: IFN therapy can effectively enhance cellular immune function, inhibit HBV replication, improve hepatic function, reduce recurrence, and improve survival in patients with HBV-related HCC after TACE treatment. The side-effects of IFN are controllable, and the treatment is safe and effective.