Given the increased difficulties of conducting research in the pediatric population, it can take a long time for pediatric patients to benefit from the research advances demonstrated in adults. Fortunately, with hepatitis B virus (HBV) the lag time has not been excessive. A specific example has been a recent study demonstrating the effectiveness of tenofovir in the pediatric population (Hepatology 2012; 56: 2018-26).
In this double-blind, placebo-controlled study, adolescents with chronic HBV were randomized into tenofovir 300 mg (n=52) or placebo (n=54) once daily for 72 weeks. 101 patients completed the 72 weeks of treatment. In this population, 85% had received prior HBV therapy and 91% were HBeAg-positive at baseline. Patients included in the study had to have ALT >2 x ULN or history of this w/in 24 months along with HBV DNA>10 to the 5th copies/mL. The inclusion criteria required a weight of >35 kg.
- Virologic response (HBV DNA <400 copies/mL): 89% in tenofovir group and 0% in placebo group
- No resistance noted through 72 weeks. All cases of virologic breakthrough were associated with non-adherence but no genotypic or phenotypic resistance.
- Normalization of ALT: among patients with baseline elevation, normalization occurred in 74% of tenofovir group compared with 31% of placebo group
- Serologic response: 21% of tenofovir group and 15% of placebo group experienced loss of HBeAg by week 72
- Adverse effects were more frequently noted in placebo group. No patients met the safety endpoint of a 6% decrease in spine bone mineral density
Since suppression of HBV DNA is a limited surrogate endpoint for the development of long-term sequelae much longer followup is needed to determine the impact of this nucleotide analogue. In adults, this agent has been associated with reversal of cirrhosis.
Across the globe, 350 million people live with chronic HBV infection and 600,000 die each year due to HBV infection. About 25% of children with HBV develop cirrhosis or cancer of liver later in life. Given the magnitude of the problem, the most promising approach remains prevention with vaccination. Treatment to prevent complications in those already infected is likely to be offered to a tiny fraction of those who might benefit.
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