Combination of Entecavir/Peginterferon Alfa‐2a in Children With Hepatitis B e Antigen–Positive Immune Tolerant Chronic Hepatitis B Virus Infection

Abstract

The optimal management strategy for children with immune‐tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune‐tolerant phase of HBV infection. Children with immune‐tolerant features of chronic hepatitis B (CHB) received entecavir once‐daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa‐2a (180 µg/1.73m2 subcutaneously) once‐weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable hepatitis B e antigen (HBeAg) with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range, 3.4‐17.9) years, were enrolled. All were positive for hepatitis B surface antigen (HBsAg) and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty‐five children completed the entire 48‐week course of therapy. At 48 weeks after treatment ended (week 96), 2 children (3%) achieved the primary endpoint and were also HBsAg negative and anti–hepatitis B surface antigen antibody (anti‐HBs) positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72, which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty‐seven children experienced adverse events (AEs), and 1 had a serious AE (SAE). Conclusion: The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune‐tolerant phase of HBV infection, and treatment was associated with frequent AEs.

Immune‐Tolerant Hepatitis B: Maybe a Misnomer but Still Hard to Treat

“…(3) In the current issue, Rosenthal et al report a study of entecavir administered for an initial 8 weeks with the addition of pegylated interferon for the subsequent 40 weeks in 60 children with IT chronic HBV. (4) Disappointingly, only 2 (3%) reached the primary endpoint of HBeAg loss and durable HBV DNA suppression ≤1,000 IU/ mL, although both also lost HBsAg. Two additional children also cleared HBeAg but did not return for their final study visit, so it is possible that they also met the study endpoints.…”

“…Poddar et al reported similarly encouraging results using the same combination regimen in 24 IT children with chronic HBV . In the current issue, Rosenthal et al report a study of entecavir administered for an initial 8 weeks with the addition of pegylated interferon for the subsequent 40 weeks in 60 children with IT chronic HBV . Disappointingly, only 2 (3%) reached the primary endpoint of HBeAg loss and durable HBV DNA suppression ≤1,000 IU/mL, although both also lost HBsAg.…”

CON: All Patients With Immune‐Tolerated Hepatitis B Virus Do Not Need to Be Treated

“…23,30 Pegylatedinterferon (PEG-IFN) and NAs inhibit HBV replication, but they do not eradicate HBV and rarely achieve the goal of HBsAg clearance. 31 Chan et al 32 studied 126 adults with IT HBV who received tenofovir disoproxil fumarate with or without 33 found only a 3% response rate in IT children treated with PEG-IFN and entecavir. Viral relapse occurred in all patients when treatment was stopped and was not accompanied by ALT flares.…”

Hepatitis B und C bei Kindern und Jugendlichen

“…Rosenthal et al publizierten aktuell eine klinische Studie ebenfalls mit Peginterferon-α2a in Kombination mit Entecavir und erreichten den primären Endpunkt, die anti-HBe-Serokonversion nach 48 Wochen, nur bei 3 % der behandelten Kinder. Daher wird eine Therapie in der immuntoleranten Phase weiterhin nicht empfohlen [15].…”