Efficacy of interferon therapy in patients with hepatitis B virus‐related primary hepatic carcinoma after transcatheter arterial chemoembolization
Authors: Xin Meng , Feng Dongfeng , Yin Beibei , Li Yan 
Published: September 2018

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.