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Chronic hepatitis B virus (HBV) remains a significant worldwide problem despite the introduction and use of hepatitis B vaccines for four decades. HBV morbidity and mortality account for millions of dollars and immeasurable suffering. Chronically infected children are at increased risk to develop liver disease and hepatocellular carcinoma. So what can we do to alter unfavorable outcomes? We know from adult studies that suppression of viral loads translates into improved outcomes; adapting this approach to children and adolescents should theoretically have similar advantageous results. In this issue of HEPATOLOGY, Murray et al.1 report on the favorable results of a randomized, placebo-controlled trial of tenofovir disoproxil fumarate (DF) in adolescents (12 to <18 years of age) with chronic hepatitis B. Subjects were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. As might be anticipated, a virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. The authors concluded that tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy.

There are several potential limitations of this study. Most of the subjects enrolled in this study were Caucasian patients from Poland and had HBV genotypes A and D. In the United States, genotypes A and C are most common, so whether these results translate into similar findings in adolescents with genotype C is currently unknown.2 Tenofovir DF has been associated with decreased bone density and osteoporotic fracture risk in human immunodeficiency virus–positive patients.3 Over 72 weeks of therapy, no significant decrease in spine bone mineral density was observed, but whether this observation will persist in adolescents with chronic HBV after a longer period of use of tenofovir DF is not known.

It is quite gratifying to witness the continued pipeline of pharmaceuticals to combat HBV infection being studied and ultimately receiving approval for use in children and adolescents. It was not that long ago that there were no approved medications or very few limited drugs to treat HBV. Although universal use of HBV vaccine will ultimately prove to be the single greatest public health measure to combat chronic HBV infection, for those unfortunate children and adolescents afflicted with the disease, medications such as tenofovir DF hold the promise of allowing long and healthy lives. Although this study was limited to adolescents, future study of tenofovir DF in younger children is being initiated. Many questions regarding the best therapy for patients with chronic HBV infection remain: Are there combinations of drugs that will improve seroconversion? Are there regimens that will allow shorter duration of therapy? Are there different regimens that will improve virologic responses in different genotypes? Does early age treatment decrease the risks of future hepatocellular carcinoma occurrence? Do quantitative hepatitis B surface antigen measurements better predict response to therapy? Certainly, continued investigations with new drugs and regimens will answer these important questions. Eradication of chronic HBV infection is closer than ever.

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