Infants diagnosed with hepatitis B virus (HBV) infection who were treated with antiviral therapy within the first 12 months of life demonstrated marked rapid HBV surface antigen (HBsAg) loss when compared with those left untreated during the first year, according to a report published in the Journal of Hepatology.
Despite the morbidity associated with chronicity, there has been little research into seroconversion with antiviral therapy administered to patients with infantile HBV, and no specific guidelines regarding treatment of this population have been established. Investigators sought to evaluate the safety and efficacy of early antiviral treatment for infants with HBV, in a first of its kind study.
Between 2010 and 2017, a prospective cohort study enrolled consecutive Chinese infants <1 year of age who were infected with HBV and who had received postnatal immunoprophylaxis but still had high viral loads, presence of serum HBsAg, and persistent alanine aminotransferase elevation equal to or more than twice the upper limit of normal (40 U/L). A total of 29 infants were divided into 2 groups based on parental treatment decisions: group I (n=18; 61.1% male; median age at diagnosis, 6 months) comprised those treated with lamivudine (4 mg/kg daily) within the first year, while group II (n=11; 90.9% male; median age at diagnosis, 7 months) consisted of patients who did not receive any antiviral therapy in the first year and were treated with interferon-α (3-5 MU/m2 every other day) after 1 year.
All participants were monitored every 3 months using a viral profile that included HBsAg quantification, with the primary outcome being the rate of loss of serum HBsAg after 12 months of therapy. Statistical differences between groups were assessed using the log-rank test.
Baseline characteristics were similar in the 2 groups, without significant differences. Cumulative serum HBsAg loss rates in group I were 39%, 67%, 78%, and 83% at 3, 6, 9, and 12 months of treatment, respectively. In group II, at the same therapeutic time points, the respective rates of cumulative serum HBsAg loss were 18%, 27%, 27%, and 36%. At 12 months, there was a significant difference between the groups in terms of HBsAg loss rates (P =.0169). In longer-term follow-up past 12 months, significant group differences in loss rates remained, with group I seeing greater and more rapid HBsAg loss over time (P =.0023).
No group II infants showed spontaneous HBsAg loss within the first year of life prior to treatment; 9 group I infants had reached this benchmark at 12 months of treatment, representing a significant difference between groups (P =.0052). After 12 months of therapy, all study participants had achieved undetectable viral loads, regardless of group.
The most frequent adverse event was fever, and there were no serious Adverse events reported during the study. There was no evidence of lamivudine resistance or virologic breakthrough during the study.
Study strengths included a well-characterized cohort. Study limitations included a small sample size.
“Therefore … antiviral treatments in HBV-infected infants with elevated [alanine aminotransferase] levels and high viral load should be considered,” noted the authors, adding, “Timing of treatment is a critical decision in order to maximize therapeutic benefit.” They recommended that future research involve larger trials aimed at validating their findings.
Funding and Conflicts of Interest Disclosures:
This study was funded by Beijing Municipal Science and Technology Commission (No. Z181100001718035) and China National Natural Science Foundation (No. 81501652).
There were no conflicts of interest declared.
Zhu S, Dong Y, Wang L, Liu W, Zhao P. Early initiation of antiviral therapy contributes to a rapid and significant loss of serum HBsAg in infantile-onset hepatitis B [published online June 19, 2019]. J Hepatol. doi:10.1016/j.jhep.2019.06.009