A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone.
BACKGROUND
Conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection.


OBJECTIVE
To evaluate the efficacy and safety of pegylated interferon-alpha2b and lamivudine combination therapy for chronic hepatitis B.


METHODS
Randomized, controlled, open-label trial.


METHODS
Outpatient clinic in a referral center.


METHODS
100 treatment-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and moderately elevated alanine aminotransferase levels.


METHODS
The primary end point was sustained virologic response (HBeAg seroconversion and HBV DNA level < 500,000 copies/mL) at 24 weeks after cessation of treatment.


METHODS
A staggered regimen of combination therapy with pegylated interferon-alpha2b (1.5 microg/kg of body weight per week; maximum, 100 microg) given for 32 weeks plus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of the 100 participants, 96% completed treatment and 80% completed post-treatment follow-up.


RESULTS
The rate of sustained virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed that, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage points (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DNA (3.91 log10 copies/mL vs. 2.83 log10 copies/mL); and less often had lamivudine-resistant mutants (21% vs. 40%). The percentages of patients with normalization of alanine aminotransferase levels and histologic improvement did not differ. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy.


CONCLUSIONS
This study lacked a double-blind design and was conducted at 1 institution. Because of the staggered pegylated interferon-lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy.


CONCLUSIONS
In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-alpha2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.
Chan
Henry Lik-Yuen
HL
Chinese University of Hong Kong and Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.
Leung
Nancy Wai-Yee
NW
Hui
Alex Yui
AY
Wong
Vincent Wai-Sun
VW
Liew
Choong-Tsek
CT
Chim
Angel Mei-Ling
AM
Chan
Francis Ka-Leung
FK
Hung
Lawrence Cheung-Tsui
LC
Lee
Yuk-Tong
YT
Tam
John Siu-Lun
JS
Lam
Christopher Wai-Kei
CW
Sung
Joseph Jao-Yiu
JJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D019562:Viral Load
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; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b