Hepatitis C, liver transplantation, and why we should consider children separately

Abstract

According to 2005 data from the Organ Procurement and Transplantation Network, hepatitis C is the leading indication for liver transplantation, accounting for more than 40% of cases. Among adults, 95% of transplanted livers are reinfected after surgery. Reinfection and progression of fibrosis in the new liver are associated with genotype, viral load, immune state, and age of the donor. In teasing out the factors that lead to reinfection, rarely is the age of the recipientmentioned. Yet as we have come to know hepatitis C, we have found that it is clearly an immune-mediated disease, with many disease features influenced by age, and thus facts stated for adults do not necessarily hold for children. Whereas transplantation for hepatitis C has been the center of many adult-focused studies, there is a paucity of equivalent information in the pediatric population. The NHANES III study estimates that 250,000 children in the United States are suspected of having hepatitis C. Because the disease often goes undetected, the number may be larger. The majority of children with hepatitis C have a relatively benign course before reaching adulthood. Liver enzymes are often normal, and rarely is there progression to cirrhosis. Autoimmune features such as cryoglobulinemia, vasculitis, and porphyria cutanea tarda are exceedingly rare. However, sometimes the disease is more aggressive, as in the case of the children presented by Barshes et al. in this issue. Certain aspects of hepatitis C are distinctly different in children compared with adults; for that reason, it is important to present and analyze pediatric data separately. The mode of acquisition, the ability to spontaneously clear the virus, and the response to antiviral therapy all differ. The most common modes of acquisition for children are maternal-fetal transfer or exposure to blood products, usually related to a comorbid process such as hemoglobinopathy or cancer. Maternal-fetal transfer depends on maternal immune state and the mother’s viral titers at the time of delivery. Transfer in healthy women ranges 1-7%, but it increases to 20% in the presence of coinfection with human immunodeficiency virus. However, unlike adults, and unlike children with hepatitis B, children who acquire this disease early in life have a good chance of clearing this virus. Ceci et al. report that up to 75% clear the virus by 2 years. Furthermore, the course in neonatal-acquired hepatitis C virus is slowly progressive, with little, if any, marked liver damage. Despite this optimistic data, hepatitis C is such a common disease that many children in the United States become chronically infected. As such, a number of patients will present with a more virulent course before adulthood. Children who acquire the disease through blood products have a different course. For these children, progression of fibrosis is tied to the underlying comorbidity. We suspect this by comparing data published regarding transfusion-acquired hepatitis C among different diseases. Transfusion-acquired hepatitis C after cardiac repair in infants tends to have a benign course, as shown by both Vogt et al. and Matsuoka et al., whereas transfusion-acquired hepatitis C for thalassemia and childhood cancers can have a much more aggressive course. Among the hemoglobinopathies, the accelerated rate of fibrosis parallels the degree of iron overload. In cancer, it is probably related to chemotherapy, radiation, and immune state. Response to treatment in children is surprisingly different than in adults. A meta-analysis of pediatric studies published between 1990 and 2000, before any multicenter large studies had been conducted, showed a sustained viral response (SVR) of 36% for monotherapy with interferon. Adults treated comparably only have 7-15% SVR. A more recent study in children aged