Treating children with HBeAg-positive chronic hepatitis B: No small accomplishment

Abstract

Despite the introduction of a highly effective hepatitis B virus(HBV) vaccine and hepatitis B immunoglobulin, mother-to-childtransmission unfortunately remains a leading cause of HBV infec-tion in children. Non-response to standard vaccines occurs inapproximately 5–10% of appropriately immunized cases, and isprobably due to very early (transplacental/intrauterine) infection.Emergence of escape mutants (mutations in the “s” gene of HBVcausing conformational changes in the “a” determinant) insteaddoes notappeartobeamajorthreat.Therecentrecommendationofprescribing Tenofovirdisoproxiltohighlyviremicpregnantwomenin the third trimester is another still missed goal to reduce therisk of perinatal transmission of HBV [1]. These situations appeareven more serious in developing countries where HBV infectionis endemic, and where a significant percentage of the populationsimply may not have access to the vaccine or cannot return for therequired booster doses [2].Children with chronic hepatitis B (CHB) when tested are mostlyin the so-called “immune-tolerant phase” (normal or mildly ele-vated aminotransferase levels, minimal histological activity, highserum HBVDNAlevels,HBeAgandHBsAgpositive).Datashowthatup to one seventh of infected children spontaneously lose theirHBeAg every year so that most become “inactive” carriers beforeadulthood [3].Because of its asymptomatic course, in general pediatric CHBis thought to require a conservative approach to therapy. Recentguidelines and expert opinions [1,4–6] agree that treatment indi-cations shouldbeverycarefullyevaluated.Childreninfectedwitharapidly replicating virus causing extensive liver damage when theimmune system attacks infected hepatocytes might represent anindication forimmediatemedicalintervention;however,anunfor-tunately small arsenal of drugs is currently available at this ageto halt HBV liver disease progression. Furthermore, with availabledrugs, treatmentfailureiscommonespeciallyinpatientswithveryhigh levels of HBV replication (>20,000IU/ml) and normal/near