Adding the antiviral medication, ribavirin, to interferon as a combination therapy for children with hepatitis C is "effective" and "reasonably safe", concludes a new clinical trial from the University of Florida.1
Ribavirin Rarely Studied in Children
Hepatitis C typically occurs without noticeable symptoms, wrote Regino Gonzalez-Peralta, MD, in the division of Pediatric Gastroenterology, Hepatology, and Nutrition at the University of Florida, and his colleagues. While interferon is standard treatment and provides long-term remission for anywhere from one-third to nearly half of these young patients,2 little has been known about the effectiveness of adding ribavirin to this therapy for them.
Little has also been known about the effect of interferon in children with hepatitis C, experts have stated. "Given the long life expectancy of children and their better tolerance to drugs, the long-term safety of these medications needs to be studied in children," wrote an NIH Panel that issued an HCV management consensus policy three years ago.3
The investigators initiated this study in two phases. The first involved research to look for the most optimal dose of ribavirin added to this therapy, while also studying the drug's safety and efficacy.
Fifty-six children were assigned at random in this initial phase to take interferon alfa-2b (Intron-A) along with ribavirin in varying doses for 48 weeks. During this period, the children was evaluated to determine the treatment combination's effectiveness, as well as side effects. Following the end of therapy, each child continued to be evaluated regularly for an additional 24 weeks.
SVR Achieved
At the end of this extended 24-week period, Gonzalez-Peralta and his team learned that 35 percent of the children taking the lowest dose of ribavirin (8 milligrams (mg) per kilogram (kg) of body weight) once per day, 37 percent of those taking the median dose (12 mg/kg per day), and nearly half of those taking the highest dose (15 mg/kg per day) during the study had undetectable levels of hepatitis C in their blood. Side effects were generally the same for all doses tested.
Based on this information, the physicians selected the 15 mg/kg dose for a second phase of the clinical trial.
Side Effects Checked
For this latter program, 118 children were recruited and assigned to receive doses of interferon with the 15 mg/kg dose of ribavirin. Each child was monitored regularly to evaluate viral response and check for any possible side effects. At the end of this phase of the trial, 46 percent of the children achieved a sustained virologic response (SVR), defined as undetectable levels of the virus 24 weeks after the end of therapy. However, children with genotypes 2 and 3 strains of the virus had better results than those with genotype 1. The latter genotype is the most common in adults with the disease, as well as the most difficult to treat successfully.4
In this study, 84 percent of those with genotypes 2 and 3 had an SVR, compared to just over a third of those with genotype 1, the doctors wrote.
All of the children experienced some side effects, but most were mild. Those included anemia, neutropenia, depression and suicidal thoughts. The most common side effect was flu-like symptoms, reported Gonzalez-Peralta and his co-investigators.
Side effects were managed by reducing doses of the medications; however, eight children had to stop treatment because of them.
Another side effect of this combination treatment was stunted growth, as has been reported in other studies, but growth rates caught up to where they should be after therapy ended, the researchers reported.
Other Findings
None of the African-American children in the study had an SVR after interferon/ribavirin treatment, the study authors learned. "The number of African-American children studied was too small to draw firm conclusions," the investigators wrote. However, the findings are similar to those in African-American adults taking combination treatment for hepatitis C.5
In conclusion, Gonzalez-Peralta and his associates wrote: "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. 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."
1. Gonzalez-Peralta RP, Kelly DA, Haber B et al. Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: efficacy, safety and pharmacokinetics. Hepatology 2005 Nov;42(5):1010-8.
2. Liao YR, Yen CP, Lin CC, Fu LS, Chiu CC, Chi CS. Soluble CD26/30 levels before and after treatment with interferon-alfa and ribavirin combination therapy in a pediatric hepatitis C patient. J Microbiol Immunol Infect 2004 Feb;37(1):67-70.
3. National Institutes of Health Consensus Development Conference Statement. Management of Hepatitis C: 2002. 2002 Jun 10-12. Available at: http://consensus.nih.gov/cons/116/091202116cdc_statement.htm. Accessed November 15, 2005.
4. Trepo C. Genotype and viral load as prognostic indicators in the treatment of hepatitis C. J Viral Hepat 2000 Jul;7(4):250-7.
5. Pyrsopoulos N, Jeffers L. Chronic hepatitis C in African Americans. Clin Liver Dis 2005 Aug;9(3):427-38, vii.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
