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Editor,—We read Bortolotti et al's article (
) reporting the long term effect of interferon (IFN) alpha in children with chronic hepatitis B (HBV). Briefly, a total of 107 children with chronic HBV who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 months. In the first trial 19 and 20 cases received IFN alpha at a dose of 3 and 7.5 MU/m2 three times a week for six months, respectively. In the second trial 34 cases received lymphoblastoid IFN at a dose of 5 MU/m2 for 12 weeks and 30 cases received IFN at the same dose but preceded by a four week course of prednisolone. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a mean period of 46 months without any therapy. Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. The cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). Loss of hepatitis B surface antigen (HBsAg) occurred in only four patients who responded during treatment.
We also wish to report on the long term follow up of 59 IFN responder children with chronic HBV (table 1).1-3 At the beginning of IFN therapy, all children (44 males; 74.6%) had abnormal or fluctuating transaminases for at least six months and were positive for HBV DNA. Mean age of the patients at diagnosis of chronic HBV was 6.8 (3.4) years (range 1–15). They were followed for a mean period of 19.9 (21.5) months (range 6–100) before treatment. Liver biopsy was performed on 29 patients; 15 (51.7%) had mild, 12 (41.4%) moderate, and two (6.9%) severe hepatitis. Forty three (84.3%) of 51 patients had at least one family member with positive HBV serology. Eight patients (group 1) had received IFN alpha at a dose of 10 MU/m2 three times a week for six months,1 34 (group 2) at a dose of 5 MU/m2 three times a week for six months2 or 12 months (five patients, group 3). Twelve patients (group 4) who were unresponsive to IFN therapy at a dose of 5 MU/m2 received IFN alpha again at a dose of 10 MU/m2 three times a week for six months.3Response to treatment was defined as loss of HBeAg during the treatment period or within 12 months after stopping treatment. All patients were followed for a mean period of 35.3 (10.8) months (range 18–62) after starting treatment. Thirty eight (64.5%) patients cleared HBeAg at the end of IFN therapy and 17 (28.8%) within 12 months after stopping treatment. Four (6.7%) patients were late responders (HBeAg clearance was observed between 21 and 30 months after stopping therapy). The mean period of HBeAg clearance was 8.2 (7.0) months. Within the follow up period, antibody to hepatitis B surface antigen (anti-HBs) occurred in seven (18.4%) patients who responded during therapy and all but one lost HBsAg. After HBeAg clearance, anti-HBe seroconversion and loss of HBV DNA was observed in all patients. Alanine aminotransferase values normalised in 98.3% of patients. None had biochemical or serological relapse within the follow up period.
The majority of our patients cleared HBV DNA and HBeAg during therapy whereas only 15% of patients in the study of Bortolottiet al responded during therapy. They followed patients for an average of 69 months and observed that all IFN responders remained HBeAg and HBV DNA negative. Although our observation period was shorter than theirs, we also observed that all responders had sustained results at the end of follow up. Similar to Bortolotti et al's results, all HBsAg cleared patients were early responders to IFN therapy in our group. In conclusion, response to IFN alpha in children with chronic hepatitis B is permanent. It is necessary to follow these patients for longer periods to see the long term effects of IFN alpha therapy, such as prevention of cirrhosis and/or hepatocellular carcinoma.
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