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

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 ≥10% if untreted 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 ≥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.