Comparison of long‐term effects of lymphoblastoid interferon alpha and recombinant interferon alpha‐2a therapy in patients with chronic hepatitis B

Summary.  To compare the long‐term effect of natural lymphoblastoid interferon‐alpha (IFN‐αnl) and recombinant IFN‐α2a therapy in patients with chronic hepatitis B, 210 patients in two trials were followed‐up for 1.1–15.5 years following the end of therapy. They included 34 patients who received placebo (control), 67 treated with IFN‐αnl (36 after prednisolone priming) and 109 treated with IFN‐α2a (56 after prednisolone priming). The cumulative sustained response was higher in patients who had been treated with IFN‐αnl after prednisolone priming than was exhibited using IFN‐αnl alone, IFN‐α2a alone or the placebo (P < 0.05), or IFN‐α2a following prednisolone priming (P = 0.052) at the end of 11 years. Hepatocellular carcinoma (HCC) was detected in 1.5% of the IFN‐αnl group, 3.7% of the IFN‐α2a group and 14.7% of the control group (control vs IFN‐αnl or IFN‐α2a, P < 0.05). The cumulative HCC development was higher in the control group than in the IFN‐αnl group (P < 0.002) and the IFN‐α2a group (P = 0.06). The cumulative survival rate was lower in the control group than in the IFN‐αnl group (P < 0.01) and the IFN‐α2a group (P = 0.02). Multivariate analysis revealed that IFN‐αnl therapy and female gender are significant predictors of sustained response; preexisting cirrhosis, age at entry and IFN therapy are significant factors in both HCC development and survival. In conclusion, IFN‐αnl treatment may have a better long‐term effect on hepatitis B virus (HBV) clearance than IFN‐α2a and placebo, and IFN therapy may provide better long‐term beneficial effects than placebo in terms of HBV clearance, reduction of HCC and prolonged survival.