A Controlled Trial of Recombinant Interferon-Alpha in Caucasian Children with Chronic Hepatitis B

Abstract

Twenty-four children with chronic active hepatitis due to hepatitis B virus (HBV) infection, who were positive for HB_eAg and had increased levels of transaminases, were included in a controlled study of treatment using recombinant interferon-α (rIFN-α), 10 MU/m2 body surface, intramuscularly, 3 times a week over a period of 3 months. During therapy, a significant decrease in HBV-DNAp was observed in the 12 patients treated. By the end of therapy, the HBV-DNA had disappeared in 3 children, the same occurring in 1 child (33 % overall) during the course of the 4th month. By this time, all the controls remained with HBV replication markers (p < 0.05). The 4 treated patients who responded became HB_eAg-negative, developing anti-HBe during the first 12 months after therapy. In the control group, the HBV-DNA disappeared in 3 children in the 7th month of follow-up. All of the children remained HB_sAg-positive. The therapy with rIFN-α was well tolerated, secondary effects consisting of a flu-like syndrome and a slight decrease in leukocytes and platelets. At the second biopsy, 15 months after the beginning of therapy, a significant decrease in Knodell’s index of histological activity was observed in the responders. In the light of these results and since treated children lost viral replication markers in a shorter period of time than the controls, who seroconverted spontaneously, we consider that rIFN-α may be useful in the treatment of chronic heptitis B in childhood.

Recombinant alpha-2a interferon treatment in a child with T-cell leukemia and chronic hepatitis B

“…About one third to two thirds of these patients achieve a protective concentration of anti-HBs [2,4,12]. After chronic HBV infection was documented in our patient, we started a-IFN treatment, since a-IFN can be used in the treatment of chronic HBV infection [16,23,27,28]. In our patient elimination of HBe Ag and HBV DNA occurred, and serum alanine aminotransferase levels decreased to normal limits following a-IFN treatment.…”

“…The recommended dose of recombinant a-IFN is 5-10 million units/m 2 given three times a week for 6 months for chronic HBV infection [28]. When we began to use a-IFN for our patient's chronic HBV infection we started with a dose of 5 million units/m 2 , and then, according to his insufficient response we increased the dosage to 10 million units/m 2 .…”

“…We did not increase the dosage any more because we obtained a good result in chronic HBV infection, and with higher levels of a-IFN, hematologic and hepatic toxicity could have occurred. Although we started a-IFN therapy for chronic HBV infection and duration of therapy is usually 6-9 months for this condition [23,28,32], we used a-IFN therapy for 18 months as reported in the literature for T-cell ALL [18]. In addition to a-IFN, we continued to administer monthly pulses of vincristine.…”

“…Chronic HBV infection affects the treatment of the primary disease, since severe hepatotoxicity may occur [22]. During the past decade, several randomized controlled trials have demonstrated favorable results with alpha-interferon (a-IFN) therapy in patients with chronic hepatitis B [16,23,28,32]. Also some clinical trials with a-IFN produced hemotologic and cytogenetic remissions in lymphoproliferative and myeloproliferative disorders [5,9,10,15,26,29].…”

Levamisole and interferon in children with chronic hepatitis B

“…Under the assumption that children treated with IFN alone show a 40% response (1,2) and with the expectation of a 60% response with IFN plus levamisole, 48 patients were necessary in each group to detect a significant difference at the 5% level, taking into account a possible drop-out rate of 2%.…”