Entecavir combined with interferon-alpha is superior to entecavir monotherapy in reducing hepatic and extrahepatic cancer in patients with chronic hepatitis B

Background The objective of this study was to assess whether entecavir (ETV) in combination with interferon-alpha (IFN-alpha) could reduce hepatocellular cancer (HCC) and extrahepatic cancers (EHCs) in patients with chronic hepatitis B (CHB). Methods The cohort consisted of 4194 patients with CHB treated with ETV combined with IFN-alpha or ETV monotherapy at a tertiary hospital in Beijing, China, from January 2009 to December 2017. The risks, hazard ratios (HRs), and 95% confidence intervals (CIs) of HCC and EHCs were compared in the 2 groups. Results In a multivariate Cox regression analysis, a significantly lower risk of HCC (HR, 0.6; 95% CI, 0.3-0.9; P = .0310) and a marginally significantly lower risk of EHCs (HR, 0.2; 95% CI, 0.02-1.3; P = .0854) were observed in the group receiving ETV combined with IFN-alpha in comparison with the ETV monotherapy group. The annual virological response rates were significantly higher in the combination therapy group versus the monotherapy group (33.8% vs 21.2%; P < .0001), but the hepatitis B surface antigen (HBsAg) seroclearance rates were not (1.2% vs 0.9%; P = .8537). The HRs were consistent with propensity score-based matching, inverse probability weighting adjustments, and adjustments for virological response and HBsAg seroclearance. Conclusions ETV combined with IFN-alpha therapy is superior to ETV monotherapy in reducing the risk of HCC and EHCs for patients with CHB. People who can tolerate and benefit from IFN-alpha therapy could consider combination therapy.