Virological response to different combination regimes of peginterferon alpha-2b and lamivudine in hepatitis B e antigen positive chronic hepatitis B.
OBJECTIVE
To investigate whether simultaneous commencement of peginterferon alpha-2b and lamivudine treatment has more potent hepatitis B virus (HBV) DNA suppression than staggered regimes.


METHODS
Thirty HBeAg-positive chronic hepatitis B patients were randomized in 1:1:1 ratio to 32-week peginterferon started simultaneously with lamivudine (group 1), eight weeks before lamivudine (group 2) or eight weeks after commencement of lamivudine (group 3). All patients received lamivudine until week 104.


RESULTS
At week 52, the log HBV DNA reduction in group 1 (6.38) was more profound than that in group 2 (3.43, P = 0.022) and tended to be superior to that in group 3 (4.44, P = 0.060). HBeAg seroconversion developed in six (67%) patients in group 1, three (33%) patients in group 2 (P = 0.35 versus group 1) and one (10%) patient in group 3 (P = 0.037 versus group 1). At week 104, the log HBV DNA reduction in group 1 (6.13) versus that in group 2 (5.24) and group 3 (5.15) was insignificantly different. Lamivudine resistance was found in four (14%) patients at week 104. There was 1.22 and 2.52 median log reduction in covalently closed circular DNA and total intrahepatic HBV DNA, respectively, at week 104, but there was no difference among the three groups. At 24 weeks post-treatment, sustained HBeAg seroconversion was observed in five (56%), three (33%) and four (40%) of the patients in groups 1, 2 and 3, respectively (P > 0.05).


CONCLUSIONS
Simultaneous commencement of peginterferon and lamivudine tend to provide more profound viral suppression than staggered regimes in the early phase of treatment.
Chan
Henry Lik-Yuen
HL
Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. hlychan@cuhk.edu.hk
Wong
Vincent Wai-Sun
VW
Chim
Angel Mei-Ling
AM
Choi
Paul Cheung-Lung
PC
Chan
Hoi-Yun
HY
Hui
Alex Yui
AY
Wong
Grace Lai-Hung
GL
Sung
Joseph Jao-Yiu
JJ
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b