In the United States based on NHANES seroprevalence studies conducted from 1988-94, an estimated 3.9 million people are infected with HCV. The NHANES found seroprevalence of 0.17% in children between 5-11 years , 0.39% in children 11-14 years. Combining these figures with the number of children in the 1990 US census, suggests that there are about 150,000 children in the U.S infected with HCV. Although chronic HCV infection in adults is the leading cause for cirrhosis and hepatocellular carcinoma, in short a major public health problem, little is known about the natural history of HCV infection in children. Although some believe that HCV infection in childhood is asymptomatic others have shown that chronic active hepatitis and cirrhosis may occur in childhood. Chronic HCV has been associated with high collagen deposition in the liver leading to fibrosis and cirrhosis. The mechanism of hepatocarcinogenesis is unclear. Hepatic 8-OH-dG is increased in adults with HCV infection. Hepatic 8-OH-dG is cleaved by endonucleases and the adduct is excreted in the urine. The rationale for focusing in children is that children are biologically naive free of alcoholism and other confounding factors. The purpose of the study is 1) to evaluate the severity of HCV infection in pediatric patients and the association with duration of infection, route of transmission, HCV genotype and liver collagen concentration 2) to characterize the natural history of chronic HCV infection in a group of chronically infected children. To better understand the pathogenesis and progression of liver disease in children with HCV it is hypothesized that the duration of infection will correlate with the following: 1) the quantity of viral RNA in the serum 2) the degree of liver injury as measured by serum alanine aminotransferase (ALT) and serum procollagen III peptide (sPIIIP), a serum marker of hepatic fibrosis. 3) the quantity of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in the urine, a non-invasive marker of hepatic oxidative DNA damage. 4) the relationship of viral genotype and viral load will be related to #2-3 The design of the study is a prospective study where children are studied at entry and in 1-1 1/2 year. The study group consists of 60 children infected with HCV and their healthy siblings. The patients are active patients in the Pediatric Liver Center and were referred for evaluation between 1992-1997. HCV infection is established by antibody to HCV (Abbott 2.0 ELISA) and PCR. The patients are between 2-29 years of age, there are 17 females and 43 males. There are 13 African American children and 47 Caucasian. Children with coinfections with hepatitis B and the human immunodeficiency virus were excluded. The following measurements are done: the patient's height, weight and a physical exam will be performed. A total of 5cc of blood is drawn for serum ALT, PIIINP, HCV viral load and genotype from each infected child. Healthy siblings are asked to participate and serve as controls. They also have height and weight and a physical exam performed and blood is sent for anti-HCV, serum ALT and sPIIIP. A spot urine collection is performed for analysis of the 8-OHdG in both HCV-infected children and controls. Both urine and blood studies are performed at baseline and in 1 year in both HCV infected and healthy controls.
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