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INTRODUCTION
HBV viral kinetics during PEG-IFN 211
Patients with HBeAg-positive chronic hepatitis B often have high levels of circulating
virus and immune responses directed against the virus cause infl ammation which in turn
may lead to cirrhosis and hepatocellular carcinoma. 1 Although treatment with nucleos(t)
ide analogues, like lamivudine, adefovir and entecavir, is effective for viral load reduction,
long-term treatment is often necessary and carries the risk of viral resistance. 2-4
Using interferon therapy, a durable treatment response can be achieved in 35-45% of
HBeAg-positive and HBeAg-negative chronic hepatitis B patients.
Pegylated interferons induce HBeAg seroconversion in approximately one third of
HBeAg-positive patients. 5-9 In a recent trial, a durable loss of HBeAg was achieved in
36% of patients after a 52 week course of PEG-IFN α-2b treatment with a 26 week followup
period. 6 The decline in viral load during PEG-IFN α-2b therapy was not uniform and
different patterns of viral decline could be recognized both during treatment and followup.
10 Remarkably, a marked viral decline between weeks 4 and 32 of treatment resulted
in the highest rate of HBeAg-loss. 10 In general, there was only minimal decline in viral
load in the fi rst month of treatment. Until now, no viral kinetics data are available during
PEG-IFN treatment in HBeAg-positive chronic hepatitis B. 11 Therefore, we analyzed the
relation between viral kinetics and pharmacokinetics of PEG-IFN α-2b in HBeAg-positive
chronic hepatitis B. To our knowledge, this is the fi rst analysis fi tting data from both
pharmacokinetics and viral kinetics during treatment in patients with chronic hepatitis B.
MATERIAL AND METHODS
Patients
A total of 96 patients who participated in an international multicenter randomized
double-blinded study reported previously6 , underwent frequent blood sampling in the
fi rst month of therapy. Eligible patients were men and women over 16 years of age
with chronic hepatitis B, documented by liver biopsy and HBsAg positivity for over six
months, and positive serum HBV DNA levels. All patients were HBeAg-positive and had
ALT levels of at least 2 times the upper limit of normal on two occasions within eight
weeks before randomization. Patients received PEG-IFN α-2b 100 μg once weekly and
were randomized to receive either lamivudine 100 mg once daily or placebo. The dose
of PEG-IFN α-2b was reduced to 50 μg once weekly after 32 weeks of therapy. Patients
were treated for 52 weeks and followed for 6 months post-treatment.