PMID- 25190434
OWN - NLM
STAT- MEDLINE
DCOM- 20150901
LR  - 20220330
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 59
IP  - 12
DP  - 2014 Dec 15
TI  - A randomized, open-label clinical study of combined pegylated interferon Alfa-2a 
      (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic 
      hepatitis B.
PG  - 1714-23
LID - 10.1093/cid/ciu702 [doi]
AB  - BACKGROUND: Treatment with pegylated interferon (peg-IFN) alfa-2a (40KD) results 
      in hepatitis B "e" antigen (HBeAg) seroconversion 6 months after treatment in up 
      to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the 
      efficacy of a novel combination of peg-IFN alfa-2a and entecavir (ETV), a potent 
      nucleoside analogue. METHODS: In total, 218 treatment-naive Chinese 
      HBeAg-positive patients were randomized to peg-IFN alfa-2a (180 microg/week) for 48 
      weeks, either as monotherapy (n = 72), or with 24 weeks of ETV (0.5 mg/daily) 
      added at week 13 (ETV add-on, n = 73), or pretreatment with a 24-week course of 
      ETV, starting peg-IFN alfa-2a at week 21 (ETV pretreatment, n = 73). The primary 
      endpoint was reduction in quantitative HBeAg from baseline to 24 weeks 
      posttreatment. RESULTS: Significant reductions in HBeAg from baseline were 
      achieved in all treatment groups 24 weeks posttreatment; reductions were 
      comparable across treatment arms (shown as log10 Paul Ehrlich international units 
      [PEIU]/mL): monotherapy: -1.4 (SD, 1.8); ETV add-on: -1.6 (SD, 1.8); ETV 
      pretreatment: -1.3 (SD, 1.7). Rates of HBeAg seroconversion were similar across 
      treatment groups posttreatment (monotherapy: 22 [31%]; ETV add-on: 18 [25%]; ETV 
      pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus 
      DNA were achieved with ETV add-on while on treatment, but were not sustained 
      posttreatment. Safety profiles were comparable between treatment groups; adverse 
      events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 
      (81%) ETV pretreatment patients. CONCLUSIONS: Neither ETV add-on nor ETV 
      pretreatment demonstrated superiority compared with 48 weeks of peg-IFN alfa-2a 
      monotherapy. The optimal treatment strategy using nucleos(t)ide analogues and 
      peg-IFN alfa-2a remains to be determined. Clinical Trials 
      Registration. NCT00614471.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the 
      Infectious Diseases Society of America. All rights reserved. For Permissions, 
      please e-mail: journals.permissions@oup.com.
FAU - Xie, Qing
AU  - Xie Q
AD  - Shanghai Ruijin Hospital, Jiao Tong University School of Medicine.
FAU - Zhou, Huijuan
AU  - Zhou H
AD  - Shanghai Ruijin Hospital, Jiao Tong University School of Medicine.
FAU - Bai, Xuefan
AU  - Bai X
AD  - Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi Province.
FAU - Wu, Shuhuan
AU  - Wu S
AD  - The First Affiliated Hospital of Zhengzhou University, Henan.
FAU - Chen, Jian-Jie
AU  - Chen JJ
AD  - Shanghai Shuguang Hospital affiliated with Shanghai University of Traditional 
      Chinese Medicine.
FAU - Sheng, Jifang
AU  - Sheng J
AD  - The First Hospital, Zhejiang University, Hangzhou.
FAU - Xie, Yao
AU  - Xie Y
AD  - Beijing Ditan Hospital.
FAU - Chen, Chengwei
AU  - Chen C
AD  - People's Liberation Army 85 Hospital, Shanghai.
FAU - Chan, Henry Lik-Yuen
AU  - Chan HL
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong.
FAU - Zhao, Mianzhi
AU  - Zhao M
AD  - Roche Pharmaceuticals Ltd, Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT00614471
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140904
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antiviral Agents)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin M)
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
MH  - Adult
MH  - Antiviral Agents/*therapeutic use
MH  - Female
MH  - Guanine/*analogs & derivatives/therapeutic use
MH  - Hepatitis B e Antigens/blood
MH  - Hepatitis B, Chronic/blood/*drug therapy/*immunology
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Immunoglobulin M/blood
MH  - Interferon-alpha/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*therapeutic use
MH  - Recombinant Proteins/therapeutic use
OTO - NOTNLM
OT  - clinical pharmacology
OT  - hepatitis B
OT  - liver
OT  - viral hepatitis
EDAT- 2014/09/06 06:00
MHDA- 2015/09/02 06:00
CRDT- 2014/09/06 06:00
PHST- 2014/09/06 06:00 [entrez]
PHST- 2014/09/06 06:00 [pubmed]
PHST- 2015/09/02 06:00 [medline]
AID - ciu702 [pii]
AID - 10.1093/cid/ciu702 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2014 Dec 15;59(12):1714-23. doi: 10.1093/cid/ciu702. Epub 2014 
      Sep 4.