Does long-term entecavir treatment really reduce hepatocellular carcinoma incidence in patients with hepatitis B virus infection?


  • Potential conflict of interest: Nothing to report.

To the Editor

I read with interest the article by Hosaka et al.[1] regarding long-term entecavir treatment in the reduction of hepatocellular carcinoma (HCC) incidence in patients with hepatitis B virus (HBV) infection. The article was a retrospective study using propensity matching based on the outcome of interest to avoid bias and concluded that long-term therapy with entecavir could reduce HCC incidence. However, some points still need further clarification.

Although the study was well matched by propensity score, the proportion of patients with alcoholism was still significantly higher in the control group. The severity of cirrhosis was not shown. It has been demonstrated that heavy alcohol consumption increases the incidence of HCC in HBV-related cirrhosis.[2] The proportion of patients with follow-up duration <1 year and incomplete sample or clinical data excluded from the study was disproportionately higher in the control group than the entecavir group. Based on the exclusion criteria, HBV patients with HCC or suspicion of HCC on enrollment were not excluded from the study. Thus, a few patients with HCC should be theoretically noted in the first year of follow-up. The diagnosis of HCC among various groups was not blinded. The duration of follow-up was significantly longer in the control group, although this had been adjusted. It appeared that very few cases developed HCC in the 1 to 2 years of follow-up. This revealed that the development of HCC was not evenly distributed in each year. All these factors may elicit significant bias between groups. It is certain that entecavir is beneficial for HBV patients to reverse fibrosis/cirrhosis3; however, the reduction of HCC incidence requires a meta-analysis with large sample size or long-term follow-up of controlled studies to be more convincing.[4, 5]

  • Gin-Ho Lo, M.D.

  • Department of Medical Research

  • Digestive Center

  • E-DA Hospital

  • Kaohsiung

  • I-Shou University

  • Taiwan