Viral hepatitis B and C in children

Abstract

Viral hepatitis B and C are the cause of significant disease worldwide. Acute infection is more common with hepatitis B than C in childhood; but chronic asymptomatic infection leading to chronic liver disease and hepatocellular carcinoma is a considerable concern. The natural history of hepatitis B is well established in adults but the long-term outcome for children is still under debate. Following an acute infection, 90% will recover spontaneously; but approximately 1% of patients develop acute fulminant hepatitis requiring liver transplantation. The main source of infection 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 10-15 years. All children with chronic hepatitis B infection should be annually monitored and those with persistent infection should be considered for anti-viral therapy. Treatment options include Interferon (5 M units per m2 subcutaneously ×3 weekly for 6 months) or Lamivudine (3 mg/kg for 12-24 months), but neither therapy is completely effective. Interferon clears viral infection in 20%-40% and is most effective in children with elevated transaminases or horizontal transmission. Only 23% seroconvert after lamivudine, 26% of whom may develop resistance with YMDD mutant variants of the hapatitis B virus. A number of other drugs, such as Adefovir Dipivoxil, Famciclovir, Entecavair and Pegylated Interferon, are under evaluation. Liver transplantation is an effective treatment for children with acute or chronic liver failure, but recurrence is high without prophylaxis. The main route of transmission for hepatitis C was originally through infected blood products or organs; but now the most common source is vertical transmission which ranges from 2%-12% depending on maternal infectivity. Breast feeding is safe in mothers with low titres of hepatitis C RNA. The natural spontaneous clearance rate for hepatitis C is between 20% and 40% and is higher in children who have been parenterally infected compared to perinatal infection. It 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 (hepatitis C RNA positive for 6 months) and evidence of histological disease should be considered for combination treatment with Pegylated Interferon (3 M units/m2 subcutaneously × 1 weekly) and oral Ribavirin (15 mg/kg) 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.