Hepatitis C is a major cause of morbidity and mortality from liver disease in adults, but it is fortunately a rare cause of liver disease in children. In population-based surveys the prevalence of antibody to hepatitis C virus (HCV) in children was found to be 0.2% to 0.4%, from which it is estimated that 60,000 to 100,000 children in the United States are chronically infected with HCV. As in adults, hepatitis C in children occurs largely in high-risk groups. The major risk factor for HCV infection in young children is perinatal exposure from an infected mother. Among adolescents, risk factors also include injection drug use and receipt of blood transfusions or blood products before 1992.
Hepatitis C is often mild and minimally progressive during childhood; cases of cirrhosis from hepatitis C have been reported but are rare. Chronic hepatitis C is an uncommon reason for liver transplantation in the pediatric age group, and several prospective as well as cross-sectional studies of hepatitis C in children have documented the rarity of progressive liver disease in this population.
Nevertheless, hepatitis C is a concern in pediatrics. While the disease tends to be mild, it is likely to be lifelong, raising concerns about long-term survival and health. In addition, therapy for hepatitis C is most likely to be successful in patients with early disease, before the onset of significant fibrosis or appearance of co-morbid conditions. A child with hepatitis C also must face concerns about infectivity and the possibility of spreading the infection to loved ones and future children.
Complicating the issues surrounding hepatitis C in children is the lack of information on the safety and efficacy of current therapies for hepatitis C in the pediatric age group. The combination of standard interferon alfa and ribavirin was recently approved for use in children with chronic hepatitis C who are 3 years and older. However, studies of more current regimens of therapy using peginterferon and ribavirin have not been conducted in adequate numbers of children to make rational decisions regarding therapy.
In response to these needs, the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) in collaboration with the Food and Drug Administration's Office of Orphan Products Development have funded a multicenter, randomized, controlled trial of peginterferon with or without ribavirin in children with chronic hepatitis C (Peds-C).
Major co-funding and support have also been provided by Hoffmann-LaRoche, Inc. (Nutley, NJ). The study is being conducted at 11 medical centers throughout the United States. The principal investigator is Dr. Kathleen Schwarz of the Johns Hopkins University School of Medicine. The other principal investigators and clinical centers are:
William Balistreri, Children's Hospital Medical Center, Cincinnati, OH
Regino Gonzalez-Peralta, University of Florida, Gainesville, FL
Barbara Haber, Children's Hospital of Philadelphia, Philadelphia, PA
Maureen Jonas, Children's Hospital, Boston, MA
Parvathi Mohan, George Washington University, Washington, DC
Jean P. Molleston, Indiana University, Indianapolis, IN
Karen F. Murray, Children's Hospital and Regional Medical Center, Seattle, WA
Michael R. Narkewicz, Children's Hospital, Denver, CO
Philip Rosenthal, University of California, San Francisco, CA
Lesley Smith, Columbia University Medical Center, New York, NY
Zachary Goodman (Pathologist), Armed Forces Institute of Pathology, Washington, DC
Patricia Robuck (Project Scientist), NIDDK, Bethesda, MD
The design of the study is for 112 children with chronic hepatitis C (ages 5-18 years) to be randomized to receive a 48-week course of peginterferon alfa-2a with either ribavirin or placebo. The dose of peginterferon will be 180 μg/1.73 m2 and that of ribavirin will be 15 mg/kg/d in two divided doses. Therapy will be discontinued at 24 weeks in nonresponders, defined as the persistence of HCV RNA. The primary endpoint is the absence of detectable HCV RNA in serum at least 24 weeks after completion of therapy. Children will have a liver biopsy before treatment, but follow-up biopsies are not planned. Children will be closely monitored. Major ancillary studies in this trial will focus on health-related quality of life, cognitive function, and psychosocial functioning before, during, and after therapy, with plans for long-term follow-up. Also included are measures of growth and development, diet, physical activity, and body composition. Thus, this trial will allow for a careful analysis of both short- and long-term safety and efficacy of peginterferon and ribavirin in children with hepatitis C. Referral of patients for enrollment is encouraged.