Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection

S Lin MD, I Sheen MD, R Chien MD, C Chu MD, Y Liaw MD

Liver Research Unit, Chang-Gung University and Chang-Gung Memorial Hospital, Taipei, Taiwan,

Aim and Methods: To examine the long-term effect of interferon (IFN) therapy in patients with chronic hepatitis B virus (HBV) infection, particularly on survival and hepatocellular carcinoma (HCC) prevention, 101 male patients with chronic hepatitis B in a randomized controlled trial were followed up for 1.1-13.3 years after end of therapy. They consisted of 34 patients who received placebo (control), and 67 patients treated with IFN (31 IFN alone and 36 IFN after prednisolone priming). Follow-up studies included clinical, biochemical and virological aspects and HCC screening every 3-6 months. Results: Twenty-eight (42%) of the 67 IFN treated patients and 8 (24%) of the 34 untreated patients seroconverted by the end of the trial. During follow-up, 22 (56%) of the 39 nonseroconverters in treated group and 5 (19%) of the 26 nonseroconverters in control group showed delayed sustained response (P< 0.005). The cumulative incidence of sustained response was highest in steroid priming group (p=0.049, vs IFN alone group; p=0.028, vs control group). Of responders at the end of the trial or delayed sustained responders during follow-up, HBeAg negative hepatitis occurred in 5 (39%) of 13 untreated patients as compared with 8 (16%) of 50 treated patients (P=0.067). HBsAg seroclearance occurred in one untreated patients and two treated patients during follow-up. HCC was detected in one (1.5%) of the 67 treated patients and 4 (12%) of the 34 untreated patients (P= 0.043). The interval between entry and HCC detection was 3.5 to 8.2 years. The cumulative incidence of HCC development was significantly higher in the control group than in the treated group (P=0.013). In contrast, the cumulative survival rate was higher in the treated group than the control group (P=0.018). Multivariate analysis showed that IFN therapy, preexisting cirrhosis and age at entry are significant independent factors for both survival and HCC development. Conclusions: The results suggest that interferon has long-term beneficial effect in terms of HBV clearance, reduction of HCC and prolongation of survival.

KEY WORDS: Interferon, placebo, hepatocellular carcinoma, survival, sustained response.

For more information, contact

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on chemotherapy.