PREDNISOLONE WITHDRAWAL THERAPY ENHANCES THE EFFECT OF HUMAN LYMPHOBLASTOID INTERFERON IN CHRONIC HEPATITIS-B

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: T wo hundred and thirteen patients with chronic hepatitis B were randomi sed to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 m g/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 da ily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 ev aluable patients, 33 (16.5%) were females, and 50 (25%) were male homo sexuals. Thirty three patients (16.5%) had chronic persistent hepatiti s, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active ci rrhosis. Results: Survival analysis disclosed statistically significan t effects of prednisolone pre-treatment on both HBeAg disappearance an d HBeAg to anti-HBe sereconversion (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 prednisolene patients vs. 28% of placebo patie nts (Chi-square test statistic 6.13; p=0.013). Prednisolone pre-treatm ent tended to be more effective in patients with higher transaminase l evels 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%), on e of whom received prednisolone pre-treatment, developed hepatic decom pensation with a fatal outcome while on interferon treatment. Conclusi ons: Prednisolone pre-treatment significantly enhanced the treatment e ffect of lymphoblastoid interferon in terms of HBeAg clearance and ser oconversion to anti-HBe. Treatment should be used with caution in pati ents with cirrhosis and avoided in patients showing signs, or with a h istory, of decompensated cirrhosis.