Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Abstract

Purpose: In patients chronically infected with hepatitis B virus, interferon has been used for the purpose of viral suppression by loss of hepatitis B e antigen (HBeAg) with or without seroconversion to antibody to HBeAg (anti-HBe). However, discussion about the effect of interferon on the development of hepatocellular carcinoma (HCC) has been controversial.

Methods: We conducted a meta-analysis of published studies. Eight studies were retrieved (1,303 patients), including two randomized controlled trials (RCTs) and six non-RCTs (553 patients received interferon treatment).

Results: The pooled estimate of the preventive effect of treatment was significantly in favor of interferon (risk difference -5.0%; 95% CI -9.4 to -0.5, P = 0.028). By subgroup analyses, the preventive effect of interferon treatment was shown in the Asian population (risk difference -8.5%; 95%CI -13.6 to -3.6, P = 0.0012), the population with the incidental rate of HCC >or=10% if untreated with interferon (risk difference -9.4%; 95%CI -14.2 to -4.6, P = 0.0001), and the population with the proportion of HBeAg-positive patients to the study population >or=70% (RD -6.0%; 95%CI -11.8 to -0.2, P = 0.043). However, the preventive effect of interferon was not shown in the European population, the population with a lower incidental rate of HCC if untreated with interferon, and the population with the lower proportion of HBeAg-positive patients to the study population. An evaluation using the Begg method indicated no evidence of publication bias.

Conclusions: Interferon treatment is considered to restrain HCC development in patients with chronic hepatitis B virus infection, especially in HBeAg-positive Asians.