Hepatitis B therapy in children.
Chronic hepatitis B virus (HBV) infection is a major cause of liver disease throughout the world, leading to cirrhosis and hepatocellular carcinoma in many individuals. Children are more likely to develop chronic HBV infection as they demonstrate greater immunotolerance to the virus, and response to therapy in children remains disappointing. Three therapeutic agents for chronic HBV infection in children have been approved in the USA, including standard IFN-alpha, lamivudine and adefovir. IFN-alpha has been the most effective ( approximately 30% hepatitis B e antigen [HBeAg] seroconversion; 10% hepatitis B surface antigen [HBsAg] seroconversion), although benefits are primarily observed in children with alanine aminotransferase levels over two-times the upper limit of normal and must be weighed against significant side effects. Studies comparing the long-term outcome of chronic hepatitis B in children treated with IFN-alpha and in untreated controls show that the rate of anti-HBeAb seroconversion tends to overlap in treated and untreated patients within a few years of follow-up, suggesting that IFN-alpha simply accelerates a spontaneous event. Lamivudine's virologic response rates mirror those of IFN-alpha (23-31% HBeAg seroconversion) with easier administration and a better safety profile but lower HBsAg seroconversion (2-3%) and high rates of drug resistance. Adefovir data show low rates of resistance and a good safety profile, but virologic response was limited to adolescent patients and was lower than that of lamivudine (16% HBeAg seroconversion; <1% HBsAg seroconversion). Entecavir and tenofovir, both approved therapies for adults with chronic HBV infection, are in trials for use in children. Future therapies will probably include these agents as well as combined therapies. Finally, watchful waiting of children is an option since current therapies are only 30% effective at best, although the long-term impact of therapy in childhood on rates of cirrhosis and hepatocellular carcinoma remains unknown.
Kurbegov
Amethyst C
AC
Pediatric Gastroenterology, University of Colorado Denver School of Medicine, 2121 East La Salle, Ste 205, Colorado Springs, CO 80909, USA. kurbegov.amethyst@tchden.org
Sokol
Ronald J
RJ
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine