It has become apparent from multiple studies that hepatitis C virus (HCV) infection is very indolent and that serious sequelae (cirrhosis, carcinoma) occur in less than 10% of persons during their first 20 years of infection. It is presumed that the proportion with severe outcomes will increase as the duration of follow-up 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 3 to 8 decades for HCV infection to produce liver damage. This study is thus geared to shift attention to HCV-infected children. It is principally conducted by the Children's Hospital National Medical Center (CNMC) in Washington, DC. The DTM, NIH is a collaborating unit. The study will identify infants and children who were transfused at CNMC from 1983 to 1992, the decade just prior to second-generation anti-HCV testing. This period was selected because rates of transfusion-associated hepatitis were still high at that time and because identified subjects would be younger than 15 at the time of enrollment and thus less likely to have had sexual contact or IV drug use as confounding sources of infection. A total of 6,500 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 screen will be enrolled in long-term laboratory and clinical follow-up. 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 a 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 emphasis to pediatric populations where response rates may be higher and long-term benefit would be greater.
