Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV-related hepatocellular carcinoma for chronic hepatitis B patients at high risk RenPeipei CaoZhujun MoRuidong LiuYuhan ChenLichang LiZiqiang ZhouTianhui LuJie LiuYunye GuoQing ChenRong ZhouHuijuan XiangXiaogang CaiWei WangHui BaoShisan XuYumin GuiHonglian XieQing 2018 <p><b>Background</b>: The effect of nucleos(t)ide analogs (NAs) <i>versus</i> interferon (IFN) on the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is controversial. We assessed whether antiviral strategy affected HCC development in CHB patients at different HCC risks.</p> <p><b>Methods</b>: 1112 CHB patients with antiviral therapy were included in this retrospective study. Patients treated with NAs only were classified into NAs group (<i>n</i> = 682) while those received IFN treatment with or without NAs were defined as IFN group (<i>n</i> = 430). Propensity score matching (PSM) was applied to minimize baseline differences.</p> <p><b>Results</b>: Totally, 31 patients developed HCC during follow-up (median 5.41 years). The cumulative HCC incidence at 10 years was significantly lower in the IFN group than NAs group (2.7% <i>vs</i> 8.0%, <i>p </i>< 0.001). Similar results were obtained in the PSM-cohort. Patients with IFN-based treatment were less likely to develop HCC than those with NAs (Hazard ratio = 0.15; 95% CI 0.04–0.66; <i>p </i>= 0.012). Subgroup analyses demonstrated that this superiority of IFN in reducing HCC development was obvious in patients at high- but not low-risk of HCC.</p> <p><b>Conclusions</b>: Reduction of HCC development was more significant in CHB patients at higher HCC risk with IFN-based therapy than NAs treatment.</p>