Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.
BACKGROUND
Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response.


METHODS
307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment.


RESULTS
49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%).


CONCLUSIONS
Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
Janssen
Harry L A
HL
Department of Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. h.janssen@erasmusmc.nl
van Zonneveld
Monika
M
Senturk
Hakan
H
Zeuzem
Stefan
S
Akarca
Ulus S
US
Cakaloglu
Yilmaz
Y
Simon
Christopher
C
So
Thomas M K
TM
Gerken
Guido
G
de Man
Robert A
RA
Niesters
Hubert G M
HG
Zondervan
Pieter
P
Hansen
Bettina
B
Schalm
Solko W
SW
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b