Entecavir, Peginterferon Ineffective for Immune-Tolerant Hepatitis B in Children
Researchers report a minimal response rate with this experimental treatment, with only 2 of 60 children achieving the pre-established primary efficacy end point.
For children with immune-tolerant chronic hepatitis B virus (HBV), combination entecavir and peginterferon for up to 48 weeks rarely led to the loss of hepatitis B e antigen (HBeAg) with sustained suppression of HBV DNA levels, according to results published in Hepatology.
In addition, the results indicated that this course of treatment frequently led to adverse events. The researchers, therefore, conducted a study to evaluate “the use of a highly potent nucleoside analogue in combination with peginterferon as a means of inducing a permanent remission in immune tolerant chronic HBV infection in children.”
The study included children with immune-tolerant features of chronic HBV. Participants received entecavir 0.015 mg/kg (maximum 0.5 mg) once daily for 48 weeks. After week 8, participants also received peginterferon alfa-2a 180 μg/1.73 m2 subcutaneously once weekly through week 48.
The primary end point was lack of detectable HBeAg with HBV DNA levels ≤1000 IU/mL 48 weeks after stopping therapy.
A total of 60 children with a median age of 10.9 years (range 3.4-17.9 years) were enrolled, and 55 completed the entire 48-week course of therapy.
At week 48 after treatment ended, 3% of children (n=2) achieved the primary end point and were also negative for hepatitis B surface antigen (HBsAg) and were positive for anti-HBs.
At week 60, 1 child was HBeAg positive but HBsAg negative, and at week 72, 1 child was HBeAg negative but had been HBsAg positive at last follow-up visit.
Among the other participants, serum alanine aminotransferase and HBV DNA levels at week 96 were similar to those at baseline.
Over the study period, 37 children experienced adverse events, with 1 child experiencing a serious adverse event.
“The few responses that occurred were complete and convincing which argues for increased efforts to identify better treatments for hepatitis B that might result in cure of this infection in a higher proportion of patients including children with immune tolerant phenotype of disease,” the researchers wrote.
Rosenthal P, Ling SC, Belle SH, et al. Combination of entecavir/peginterferon alfa-2a in children with HBeAg-positive immune tolerant chronic hepatitis B virus infection [published online October 15, 2018]. Hepatology. doi: 10.1002/hep.30312