PMID- 30318613
OWN - NLM
STAT- MEDLINE
DCOM- 20200611
LR  - 20200611
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 69
IP  - 6
DP  - 2019 Jun
TI  - Combination of Entecavir/Peginterferon Alfa-2a in Children With Hepatitis B e 
      Antigen-Positive Immune Tolerant Chronic Hepatitis B Virus Infection.
PG  - 2326-2337
LID - 10.1002/hep.30312 [doi]
AB  - 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 microg/1.73m(2) 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.
CI  - (c) 2018 by the American Association for the Study of Liver Diseases.
FAU - Rosenthal, Philip
AU  - Rosenthal P
AD  - Pediatrics, University of California, San Francisco, San Francisco, CA.
FAU - Ling, Simon C
AU  - Ling SC
AD  - The Hospital for Sick Children, and Department of Pediatrics, University of 
      Toronto, Toronto, ON, Canada.
FAU - Belle, Steven H
AU  - Belle SH
AD  - Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
FAU - Murray, Karen F
AU  - Murray KF
AD  - Pediatrics, University of Washington School of Medicine and Seattle Children's 
      Hospital, Seattle, WA.
FAU - Rodriguez-Baez, Norberto
AU  - Rodriguez-Baez N
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Schwarzenberg, Sarah J
AU  - Schwarzenberg SJ
AD  - Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN.
FAU - Teckman, Jeffrey
AU  - Teckman J
AD  - Pediatrics, Saint Louis University, Saint Louis, MO.
FAU - Lin, Hsing-Hua S
AU  - Lin HS
AD  - Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
FAU - Schwarz, Kathleen B
AU  - Schwarz KB
AD  - Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
CN  - Hepatitis B Research Network (HBRN)
LA  - eng
GR  - U01 DK082916/DK/NIDDK NIH HHS/United States
GR  - Bristol Myers Squibb/International
GR  - A-DK-3002-001/NIDDK and the Center for Disease Control and 
      Prevention/International
GR  - U01 DK082871/DK/NIDDK NIH HHS/United States
GR  - U01 DK082944/DK/NIDDK NIH HHS/United States
GR  - U01 DK082864/DK/NIDDK NIH HHS/United States
GR  - Roche Molecular Systems, Inc./International
GR  - U01 DK082843/DK/NIDDK NIH HHS/United States
GR  - U01 DK 082843/DK/NIDDK NIH HHS/United States
GR  - Bristol-Myers Squibb/International
GR  - U01 DK082874/DK/NIDDK NIH HHS/United States
GR  - Genentech/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20190220
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 5968Y6H45M (entecavir)
RN  - 5Z93L87A1R (Guanine)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
CIN - Hepatology. 2019 Jun;69(6):2315-2317. PMID: 30964209
MH  - Adolescent
MH  - Antiviral Agents/*administration & dosage
MH  - Child
MH  - Child, Preschool
MH  - Drug Combinations
MH  - Female
MH  - Guanine/administration & dosage/*analogs & derivatives
MH  - Hepatitis B e Antigens/*blood
MH  - Hepatitis B, Chronic/*blood/*drug therapy/immunology
MH  - Humans
MH  - Immune Tolerance
MH  - Interferon-alpha/*administration & dosage
MH  - Male
MH  - Polyethylene Glycols/*administration & dosage
MH  - Recombinant Proteins/administration & dosage
PMC - PMC6465180
MID - NIHMS993066
EDAT- 2018/10/16 06:00
MHDA- 2020/06/12 06:00
PMCR- 2020/06/01
CRDT- 2018/10/16 06:00
PHST- 2018/06/21 00:00 [received]
PHST- 2018/10/10 00:00 [accepted]
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2020/06/12 06:00 [medline]
PHST- 2018/10/16 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 10.1002/hep.30312 [doi]
PST - ppublish
SO  - Hepatology. 2019 Jun;69(6):2326-2337. doi: 10.1002/hep.30312. Epub 2019 Feb 20.