Steroid priming does not potentiate the effect of IFN-a.
The comparative efficacy of prednisolone followed by (HEPATOLOGY 1996;23:700-707.) interferon alfa (IFN-a) versus IFN-a alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-con-Liver disease due to chronic hepatitis B virus (HBV) trolled trial was conducted in 95 hepatitis B virus (HBV)infection is potentially serious, with increased risk of DNA/hepatitis B e antigen (HBeAg)-positive children developing cirrhosis and/or hepatocellular carcinoma. 1 (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89%] To date, the most extensive clinical experience in the white), all having inflammatory changes on liver biopsy. management of this condition is with interferon alfa Patients were randomized to receive either predniso-(IFN-a). 2 The drug has been shown to accelerate the lone followed by IFN-a (n Γ
34); placebo followed by IFNrate of spontaneous loss of serum markers of HBV repa (n Γ
30); or no treatment (n Γ
31). The prednisolone/ lication, 3 thereby decreasing the amount of integrated placebo was given on a double-blind basis. Lymphoblas-HBV DNA into the host genome and possibly the risk toid IFN-a was given at 5 MU/m 2 three times a week for 12 weeks. Baseline clinical, biochemical, and histological of hepatocellular carcinoma. However, while the effifeatures were similar for the three groups. The majority cacy of interferon treatment has been well documented (85%) had a baseline aspartate aminotransferase (AST) in several controlled trials in adults, 4,5 the results in level Β°100 IU/L. On follow-up between 12 and 18 months children are less conclusive. 3,[6][7][8][9][10] This is because most (median, 15 months) after treatment, the loss of HBeAg clinical trials were performed in a small number of with anti-HBe seroconversion was more common in papatients. Furthermore, the interpretation of the data is tients pretreated with steroids (12 of 34 [35%]) or placebo complicated by variations in interferon dose schedules, [12 of 30 (40%)] as against controls (4 of 31 [13%], PΓ΅ .05). disparities in patient characteristics in terms of disease Factors predictive of anti-HBe seroconversion were activity, and/or mode of infection and differences in baseline HBV-DNA concentration of Β°1,000 pg/mL and rates of spontaneous antibody to hepatitis B e antigen a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treat-(anti-HBe) seroconversion in untreated controls. Atment with IFN-a, at the dose and duration used in this tempts to improve the seroconversion rates have used study, improves the rate of anti-HBe seroconversion. a combination treatment of prednisolone followed by interferon. 11 The withdrawal of steroids frequently results in exacerbation of symptoms, which is thought to represent an immunological rebound directed at virus Abbreviations: HBV, hepatitis B virus; IFN-a, interferon alfa; anti-HBe, infected hepatocytes. However, whereas some studies antibody to hepatitis B e antigen; HBeAg, hepatitis B e antigen; AST, asparate aminotransferase; HDV, hepatitis delta virus; anti-HBs, antibody to hepatitis have suggested that immunologic priming with ste-B surface antigen; ALT, alanine aminotransferase.
roids is beneficial, [12][13][14][15] others have not shown a signifi-From the 1 Department of Child Health and 2 Institute of Liver Studies, cantly increased response rate. 5,16,17 In the only ran-