It is apparent from multiple studies that hepatitis C virus (HCV) infection is very indolent and serious sequelae (cirrhosis, carcinoma) occur in less than 10 percent of persons during their first 20 years of infection. The proportion with severe outcomes are presumed to increase as the duration of followup increases. A corollary to these findings is that most persons who acquire this infection late in life will not be seriously affected by their HCV infection, whereas those who acquire the infection in childhood and young adulthood may be at increased risk because they will have three to eight decades for HCV infection to invoke liver damage. This study shifts attention to HCV-infected children. The study will identify infants and children who were transfused at the Children's National Medical Center (CNMC) from 1983 to 1992, the decade just prior to second generation anti-HCV testing, when rates of transfusion-associated hepatitis were still high. Identified subjects would be less than 15 years old at the time of enrollment and thus less likely to have sexual contact or intravenous drug use as confounding sources of infection. Approximately 6500 children who meet eligibility criteria have been transfused at CNMC. The entire cohort will be contacted and asked to provide a blood sample that will be tested for antibodies to HCV and hepatitis G virus (HGV). Subjects found antibody positive on initial screening will be enrolled in long-term laboratory and clinical followup. In those with biochemical evidence of chronic hepatitis, a liver biopsy may be performed. The study will determine the minimal rate of transfusion-transmitted HCV and HGV infection and will allow for an annualized incidence estimate and determination of the national burden of transfusion-induced viral hepatitis in children. Using archival samples, the study will also determine the duration of infection and the rate of viral persistence. Liver biopsy will establish the extent of disease in those chronically infected. If persistent infection and chronic liver disease are as common in children as in adults, this study will have major implications for antiviral therapy programs and might serve to shift the research emphasis to pediatric populations where response rates may be higher and long-term benefits would be greater.
