Hepatitis B and C in Children: New Therapies

Viral Hepatitis B and C cause significant disease worldwide. Chronic asymptomatic infection in childhood leads to chronic liver disease and the potential for developing hepatocellular carcinoma. The main source of infection for hepatitis B (HBV) in childhood is perinatal transmission, which is effectively prevented using vaccination, antenatal screening and screening of blood products and organ donors. The vaccine is effective in 97% of newborn infants and lasts for 10 to 15 years. All children with chronic HBV infection should be annually monitored and those with persistent infection should be considered for anti-viral therapy. Treatment options include Interferon or lamivudine, but neither therapy is effective. Interferon clears viral infection in 20 to 40% of children and is most effective in children with elevated transaminases or horizontal transmission. Only 23% of children seroconvert after lamivudine, 26% of whom may develop resistance with YMDD mutant variants of HBV. Adefovir Dipivoxil has recently been shown to have a 20% seroconversion rate with very low incidence of viral mutants at 12 months. Other drugs such as Telbivudine, and Entecavair, and Pegylated Interferon are under evaluation. Liver transplantation is effective treatment for children with acute or chronic liver failure but recurrence is high without prophylaxis with immunoglobulin, HBV vaccination and antiviral therapy. The commonest source of transmission for hepatitis C (HCV) is vertical transmission, ranging from 2-12% depending on maternal infectivity. Breast feeding is safe in mothers with low titres of HCV RNA. The natural spontaneous clearance rate for HCV is between 20 and 40% and is higher in children who have been parenterally infected compared to perinatal infection. HCV is a mild disease in children, but the indication for treatment is based on the future risk of cirrhosis and hepatocellular cancer. Children with persistent infection (HCV RNA positive for 6 months) and evidence of histological disease should be considered for combination treatment with Pegylated Interferon and oral Ribavirin which has a sustained-response rate of 80-100% for genotypes 2 and 3 and 50% for genotype 1. Liver transplantation for Hepatitis C in children is rarely required, but 100% recurrence can be expected without prophylaxis. Emerging new therapies include viral enzyme inhibitors, cytokines, antisense oligonucleosides which are at an early stage of development.