Nearly half of 118 children with chronic Hepatitis C virus (HCV) treated with a combination of interferon-alpha-2b and an optimized dose of ribavirin achieved sustained viral response, and side effects were generally mild. These results are reported in the November 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).
Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.
HCV is usually asymptomatic in children though it can lead to serious liver damage. Treatment with interferon is standard and induces lasting remission in more than a third of infected children. The addition of ribavirin to treatment with interferon has been shown to markedly improve outcomes for adults with HCV, but the combination has not been extensively studied in children. Led by Regino González-Peralta, M.D. of the Division of Pediatric Gastroenterology, Hepatology, and Nutrition at the University of Florida, researchers addressed combination therapy for children with a twofold program.
The first part searched for the optimal dose of ribavirin for children with HCV while testing the drug's safety and efficacy. Fifty-six children, ages five to 16, were randomly assigned to take interferon along with ribavirin in varying doses for 48 weeks. They were evaluated for efficacy and side effects at regular intervals, and followed-up for an additional 24 weeks. By the end of the follow-up period, 35 percent of children taking 8 mg/kg/day of ribavirin, 37 percent taking 12 mg/kg/day, and 47 percent of 15/mg/kg/day had undetectable levels of HCV in their blood. Side effects were similar among all doses. Based on this data, the researchers selected the dosage 15 mg/kg/day for further study.
In all, 118 children with HCV received the optimized treatment--interferon with 15 mg/kg/day of ribavirin. They were evaluated regularly throughout treatment and follow-up to determine viral response and assess and manage side effects. At the end of the study, 46 percent had achieved sustained viral response. Children with HCV genotype 2/3 had higher sustained virologic response rates than those with HCV genotype 1.
All subjects experienced some side effects, but most were mild, the most common being flu-like symptoms. Severe side effects included anemia, neutropenia, depression and suicidal thoughts, and one child in the study attempted suicide. The researchers responded to adverse side effects by dose modification, and 8 subjects completely discontinued treatment because of adverse events.
As in previous studies, children in this one exhibited growth inhibition while receiving the therapy, however, they typically experienced height and weight catch-up gains after it ended. Interestingly, none of the African-American children in the study had a sustained virologic response to combination therapy. "The number of African-American children studied was too small to draw firm conclusions," say the authors. But this observation matches previous reports that African-American adults have lower response rates to combination therapy.
Overall, "our studies demonstrate that interferon alfa 2b in combination with oral ribavirin is effective and reasonably safe for the treatment of childhood chronic hepatitis C," the authors conclude. Importantly, "sustained virologic response rates in children with chronic HCV given interferon alfa-2b with ribavirin in these studies are higher than in those using interferon alone."