Sir,- Dr.Lai and colleagues report a trial of 24 Chinese children with chronic hepatitis B virus (HBV) infection and active viral replication who were treated with recombinant alpha 2-interferon (rIFN-alpha) three times a week for 3 months. After follow-up for 18 months, 2 of the treated group and 2 controls became HBV-DNA negative. We have done two controlled studies.
In the first, 24 Spanish patients aged 2-23 years were randomly allocated to control (n=12) or treatment groups. The test group received 10 MU/m2 rIFN-alpha 2a ("Roferon") intramuscularly thrice weekly for 3 months. All the patients had a histological diagnosis of chronic active hepatitis and were hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA positive for at least 6 months before entry into the studdy. At the end of the treatment period, 3 treated patients became HBV-DNA negative. Another treated patient lost HBV-DNA at the 6th month. These 4 patients remained HBV-DNA negative over the rest of the 12-month follow-up. No control patient lost HBV-DNAa during the firts 6 months of study but 2 controls became HBV-DNA negative at the 9th month and another 2 at the 12 th month. 4 treated patients and 3 controls were HBeAAg negative at the 12 th month of follow-up. Alanine aminotransferase (ALT) levels decreased in the 4 treated patients but not among non-responders.
In the second trial 24 Spainsh children who were aged 4-14 years and were HBsAg, HBeAg, and HBV-DNA positive for at least 6 months before entry were randomly allocated to one of three groups: (I) control (n=8); (II) 10 MU/m2 rIFN-alpha (Boehringer Ingelheim) intramuscularly twice a week for 6 months (n=8); and (III) 7-5 MU/m2 on a similar regimen (n=8). 22 patients had chronic active hepatitis and 2 had chronic persistent hepatitis (histologically proven). The three groups were similar at baseline. During therapy, a significant decrease of HBV-DNA polymerase levels was observed among treated patients (p<0.01). At the end of therapy, 1 control patient and 4 treated patients lost circulating HBV-DNA. At the end of the study at 15 months 7 cases were HBV-DNA negative (3 controls, 2 from group II, and 2 from III). 3 patients, one from every group, were HBsAg negative 6th month and acquired antibody to HBeAg. At the 15th month follow-up, HBeAg became undertectable in 6 children (3 control group II, and 1 group III). A decrease in ALT levels among interferon responders was observed, but again not in the other case. A second liver biopsy was done in 20 children. Knodell's index decreased among responders (baseline vs final: 13 (SD 2-4) vs (3-7). In addition, liver hepatitis B core antigen decrease significantly among treated patients (p<0.05).
No intolerable toxicity was observed and all the children completed the treatment period in both studies.
The results of our two trials suggest that rIFN-alpha is a suitable treatment for hepatitis B in childhood. The infectivity period is shortened in the treated patients compared with the controls. None of our patients had reactivation of the disease, in contrast to the results of Lai et al. This could be because almost all the patients of that study had normal ALT levels and were Chines, who is known to have a poor response to antiviral therapy. Our patient had abnormal ALT levels and were Caucasian. More trials of rIFN-alpha in children with chronic hepatitis B should be considered with different doses and periods of treament.