Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.

BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B.

METHODS

Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis.

RESULTS

Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment.

CONCLUSIONS

Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.