AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in “clinically severe” exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. METHODS: Twenty-two patients, 14 men and 8 women, were defined as “severe” exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease (“early high-dose” group) and 11 patients were either treated more than 10 d or untreated with corticosteroids (“non-early high-dose” group). RESULTS: Mean age, male-to-female ratio, mean prothrombin time (FT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the “early high-dose” group survived, while only 2 of 11 patients of the “non-early high-dose” group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the “early high-dose” group. Both ALT levels and HBV DNA polymerase levels fell in both groups. CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with “clinically life-threatening” severe exacerbation of chronic hepatitis B , when used in the early stage of illness. AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes at fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in “clinically severe ” exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. METHODS: Twenty- two patients, 14 men and 8 women, were defined as “severe ” exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 days after the diagnosis of severe disease (“early high-dose” group) and 11 patients were either treated more than 10 days or untreated with corticosteroid RESULTS: Mean age, male-to-female ratio, mean prothrombin time (FT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the “early high-dose” group survived, while only 2 of 11 patients of the “non-early During the first 2 weeks after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the ”early high-dose “ group. Both ALT levels and CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with ”clinically life-threatening " severe exacerbation of chronic hepatitis B, when used in the early stage of illness.